Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
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Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\n
Thank you all for being part of the journey. 5,000 times thank you!
\\n\\n
Now with 5,000 titles available Open Access, which one will you read next?
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
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"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\n
Seeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\n
Over these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\n
We are excited about the present, and we look forward to sharing many more successes in the future.
\n\n
Thank you all for being part of the journey. 5,000 times thank you!
\n\n
Now with 5,000 titles available Open Access, which one will you read next?
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6229",leadTitle:null,fullTitle:"Kinetic Theory",title:"Kinetic Theory",subtitle:null,reviewType:"peer-reviewed",abstract:'The world is governed by motions. The term kinetics partially originated from the Greek word "kinisis," which means motion. How important is motion in our life is easily understood. But, how the kinetic theories have been developed during years? Which are the new kinetic theories and updates in recent years? This question and many others can be answered with this book. Some important areas discussed in this book are the kinetic theory of gases, kinetic theory of liquids and vapors, thermodynamic aspects, transportation phenomena, adsorption-kinetic theories, linear and nonlinear kinetic equations, quantum kinetic theory, kinetic theory of nucleation, plasma kinetic theory, and relativistic kinetic theory.',isbn:"978-953-51-3801-3",printIsbn:"978-953-51-3802-0",pdfIsbn:"978-953-51-4066-5",doi:"10.5772/intechopen.68734",price:119,priceEur:129,priceUsd:155,slug:"kinetic-theory",numberOfPages:138,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"789a1f7f0e0f9f4717d6fef84d47f013",bookSignature:"George Z. Kyzas and Athanasios C. Mitropoulos",publishedDate:"February 14th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6229.jpg",numberOfDownloads:8598,numberOfWosCitations:22,numberOfCrossrefCitations:12,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:24,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:58,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 11th 2017",dateEndSecondStepPublish:"May 2nd 2017",dateEndThirdStepPublish:"November 19th 2017",dateEndFourthStepPublish:"December 19th 2017",dateEndFifthStepPublish:"February 19th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"152296",title:"Prof.",name:"George",middleName:"Z.",surname:"Kyzas",slug:"george-kyzas",fullName:"George Kyzas",profilePictureURL:"https://mts.intechopen.com/storage/users/152296/images/system/152296.jpg",biography:"Dr. George Z. Kyzas is Associate Professor at the Department of Chemistry at the International Hellenic University (IHU). He was born in Drama (Greece) and studied Chemistry at the Department of Chemistry at the Aristotle University of Thessaloniki (AUTh). He obtained his BSc, MSc, and PhD degrees from the Department of Chemistry (AUTh) expertised in Chemical Technology. He then worked as a PostDoc Researcher at the Department of Chemistry (AUTh) in many research projects. He is now working at the Department of Chemistry (International Hellenic University, Kavala, Greece), being the Head of the Department (since 2019). He is also Director of the MSc Cosmetic Chemistry (since 2021). His research interests are the synthesis and characterization of various (majorly adsorbent) materials (inorganic, aluminates, polymers, graphenes, agro-food residues, nanomaterials, CNTs, etc.) for environmental applications (i.e. treatment of wastewaters).\nHis scientific work has been published in more than 210 Papers in international journals with a high impact factor (IF,ave 5.5), while he published 8 Books, 35 Chapters in scientific Books and holds 3 Patents. He was also 8 times Guest Editor at Special issues of journals and has more than 100 Announcements (Invited) in International Conferences. His work is widely recognized with 8,000 Citations based on Scopus database (h-index 55) and 10,000 Citations based on Google Scholar database (h-index 57).\nHis name is included in the list of World Top 2% Scientists for 2019 and 2020, which is compiled by the Stanford University (USA) based on standardized citation indicators.\nHe has been awarded with scholarships from the Research Committee of the Aristotle University of Thessaloniki (2009, 2013), the Greek State Scholarship Foundation (2013) and the Stavros Niarchos Foundation (2016). He has also participated in about 25 research projects. He is a Reviewer in more than 200 scientific journals (ACS, Elsevier, Wiley, Springer, Taylor&Francis, etc) and participates as an Assessor/Evaluator/Reviewer in National, European and International research proposals/calls/projects.",institutionString:"International Hellenic University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"152889",title:"Dr.",name:"Athanasios",middleName:null,surname:"Mitropoulos",slug:"athanasios-mitropoulos",fullName:"Athanasios Mitropoulos",profilePictureURL:"https://mts.intechopen.com/storage/users/152889/images/5607_n.jpg",biography:"Prof. A. Ch. Mitropoulos was born in Athens in 1957. He studied Chemistry at the University of Thessaloniki (BSc) and Physical Chemistry at the University of Bristol (MSc, PhD). In 1998, he was appointed as professor in the Department of Petroleum Engineering at the Eastern Macedonia and Thrace Institute of Technology. Since 2008, Prof. Mitropoulos is the president of the same institute. He specializes on the characterization of porous media, nanoporous materials and membranes with in situ techniques of adsorption, and small-angle X-ray scattering. He has more than 100 journal papers, book chapters, and patents. Prof. Mitropoulos is a member of the Society of Petroleum Engineers.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1393",title:"Kinematics",slug:"classical-mechanics-kinematics"}],chapters:[{id:"58948",title:"Introductory Chapter: Kinetics from Past to Future",doi:"10.5772/intechopen.73591",slug:"introductory-chapter-kinetics-from-past-to-future",totalDownloads:1072,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"George Z. Kyzas and Athanasios C. Mitropoulos",downloadPdfUrl:"/chapter/pdf-download/58948",previewPdfUrl:"/chapter/pdf-preview/58948",authors:[{id:"152296",title:"Prof.",name:"George",surname:"Kyzas",slug:"george-kyzas",fullName:"George Kyzas"},{id:"212796",title:"Dr.",name:"Athanasios C.",surname:"Mitropoulos",slug:"athanasios-c.-mitropoulos",fullName:"Athanasios C. Mitropoulos"}],corrections:null},{id:"56964",title:"Discrete Boltzmann Modeling of Compressible Flows",doi:"10.5772/intechopen.70748",slug:"discrete-boltzmann-modeling-of-compressible-flows",totalDownloads:1328,totalCrossrefCites:5,totalDimensionsCites:17,hasAltmetrics:0,abstract:"Mathematically, the typical difference of discrete Boltzmann model (DBM) from the traditional hydrodynamic one is that the Navier-Stokes (NS) equations are replaced by a discrete Boltzmann equation. But physically, this replacement has a significant gain: a DBM is roughly equivalent to a hydrodynamic model supplemented by a coarse-grained model of the thermodynamic non-equilibrium (TNE) effects, where the hydrodynamic model can be and can also be beyond the NS. Via the DBM, it is convenient to perform simulations on systems with flexible Knudsen number. The observations on TNE are being obtaining more applications with time.",signatures:"Aiguo Xu, Guangcai Zhang and Yudong Zhang",downloadPdfUrl:"/chapter/pdf-download/56964",previewPdfUrl:"/chapter/pdf-preview/56964",authors:[{id:"42273",title:"Prof.",name:"Aiguo",surname:"Xu",slug:"aiguo-xu",fullName:"Aiguo Xu"},{id:"110958",title:"Prof.",name:"Guangcai",surname:"Zhang",slug:"guangcai-zhang",fullName:"Guangcai Zhang"},{id:"209189",title:"Dr.",name:"Yudong",surname:"Zhang",slug:"yudong-zhang",fullName:"Yudong Zhang"}],corrections:null},{id:"58522",title:"Collective Mode Interactions in Lorentzian Space Plasma",doi:"10.5772/intechopen.71847",slug:"collective-mode-interactions-in-lorentzian-space-plasma",totalDownloads:1187,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Plasmas exhibit a vast variety of waves and oscillations in which moving charged particle produce fields which ultimately give rise to particle motion. These wave-particle effects are used in the acceleration heating methods of plasma particles, and in wave generation as well. Plasmas are often manipulated with EM waves, e.g., Alfvén waves are long-wavelength modes (drift-waves) where fluid theory is most reliable, while for short wavelength modes (e.g., Kinetic Alfvén waves), collisionless effects becomes important. In this chapter, the properties of kinetic Alfvén waves are aimed to study by employing two potential theory by taking particle streaming and Weibel instability with temperature anisotropy in a Lorentzian plasma.",signatures:"Nazish Rubab and Sadia Zaheer",downloadPdfUrl:"/chapter/pdf-download/58522",previewPdfUrl:"/chapter/pdf-preview/58522",authors:[{id:"209551",title:"Dr.",name:"Nazish",surname:"Rubab",slug:"nazish-rubab",fullName:"Nazish Rubab"},{id:"210810",title:"Dr.",name:"Sadia",surname:"Zaheer",slug:"sadia-zaheer",fullName:"Sadia Zaheer"}],corrections:null},{id:"57137",title:"Kinetic Theory of Creep and Long-Term Strength of Metals",doi:"10.5772/intechopen.70768",slug:"kinetic-theory-of-creep-and-long-term-strength-of-metals",totalDownloads:1185,totalCrossrefCites:5,totalDimensionsCites:5,hasAltmetrics:0,abstract:"This chapter deals with the simulation of the creep process and the effect of long-term strength of metals, notably, in both uniaxial and complex stress states. A description of a creep experiment and the simplest creep models are presented, that is, the theory of steady creep, the theory of ageing, the theory of flow and the theory of hardening. In creep process simulation, a kinetic theory based on the introduction of structural parameters characterising the state of the metal at a given time is widely used. Among such parameters, metal damage in the creep process, work of stresses on creep deformations (energy version) and concentration of an aggressive medium in the metal were studied. The coupled problem of creep and long tensile strength is also considered taking into account the mutual influence of damage accumulation and one-dimensional diffusion of the aggressive medium. The times to fracture are determined both in the presence of an aggressive medium and in the absence of one. A significant contribution of Soviet (Russian), European, American and Japanese scientists to the development of continuum damage mechanics is highlighted.",signatures:"Alexander Lokoshchenko and Leonid Fomin",downloadPdfUrl:"/chapter/pdf-download/57137",previewPdfUrl:"/chapter/pdf-preview/57137",authors:[{id:"215612",title:"Prof.",name:"Leonid",surname:"Fomin",slug:"leonid-fomin",fullName:"Leonid Fomin"},{id:"215613",title:"Prof.",name:"Alexander",surname:"Lokoshchenko",slug:"alexander-lokoshchenko",fullName:"Alexander Lokoshchenko"}],corrections:null},{id:"56946",title:"Kinetic Equations of Active Soft Matter",doi:"10.5772/intechopen.70667",slug:"kinetic-equations-of-active-soft-matter",totalDownloads:1182,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"We consider a new approach to the description of the collective behavior of complex systems of mathematical biology based on the evolution equations for observables of such systems. This representation of the kinetic evolution seems, in fact, the direct mathematically fully consistent formulation modeling the collective behavior of biological systems since the traditional notion of the state in kinetic theory is more subtle and it is an implicit characteristic of the populations of living creatures.",signatures:"Viktor Gerasimenko",downloadPdfUrl:"/chapter/pdf-download/56946",previewPdfUrl:"/chapter/pdf-preview/56946",authors:[{id:"211077",title:"Prof.",name:"Viktor",surname:"Gerasimenko",slug:"viktor-gerasimenko",fullName:"Viktor Gerasimenko"}],corrections:null},{id:"56993",title:"Non-Linear Kinetic Analysis of Protein Assembly Based on Center Manifold Theory",doi:"10.5772/intechopen.70750",slug:"non-linear-kinetic-analysis-of-protein-assembly-based-on-center-manifold-theory",totalDownloads:910,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This review introduces a novel mathematical description of protein assembly. Protein assembly occurs in a substantially open non-equilibrium and non-linear kinetic system. The goal of systems biology is to make predictions about such complicated systems, but few have conducted stability analysis for given systems. Particularly, simulated dynamic behaviors have not been sufficiently verified by kinetic analysis in predicting macromolecular protein interactions and assembly. The non-linearity of protein assembly kinetics is complex, and it is very difficult to determine a model of multi-protein interactions based on numerical calculation. We studied the non-linear kinetics involved in the diffusion process of proteins consisting of two or three species of macromolecules and set a novel model in which non-linearity is given by the diffusion coefficient that depends on the protein concentration. By making the diffusion coefficient concentration-dependent, non-linearity leads to a simple system model. Protein assembly is initiated by monomeric protein interactions and regulated by cofactors such as guanidine triphosphate (GTP) or adenosine triphosphate (ATP) binding to the monomer. This cofactor concentration promotes the dynamic behavior of protein assembly and can be treated as an order parameter. Further, kinetic stability analysis in the center manifold theory (CMT) is introduced for analyzing the behavior of the system around the critical state. Although CMT has not been sufficiently applied for stability analysis of protein assembly systems, this theory predicts the dynamic behavior of the assembly system around the critical point using concentration as a cofactor. Protein assembly theory will provide a novel framework for nonlinear multi-parametric analysis.",signatures:"Tatsuaki Tsuruyama",downloadPdfUrl:"/chapter/pdf-download/56993",previewPdfUrl:"/chapter/pdf-preview/56993",authors:[{id:"94907",title:"Prof.",name:"Tatsuaki",surname:"Tsuruyama",slug:"tatsuaki-tsuruyama",fullName:"Tatsuaki Tsuruyama"}],corrections:null},{id:"57376",title:"Plasma Kinetic Theory",doi:"10.5772/intechopen.70843",slug:"plasma-kinetic-theory",totalDownloads:1734,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The description of plasma using fluid model is mostly insufficient and requires the consideration of velocity distribution which leads to kinetic theory. Kinetic theory of plasma describes and predicts the condition of plasma from microscopic interactions and motions of its constituents. It provides an essential basis for an introductory course on plasma physics as well as for advanced kinetic theory. Plasma kinetics deals with the relationship between velocity and forces and the study of continua in velocity space. Plasma kinetics mathematical equations provide aid to the readers in understanding simple tools to determine the plasma dynamics and kinetics as described in this chapter. Kinetic theory provides the basics and essential introduction to plasma physics and subsequently advanced kinetic theory. Plasma waves, oscillations, frequencies, and applications are the subjects of kinetic theory. In this chapter, mathematical formulations essential for exploring plasma kinetics are compiled and described simplistically along with a precise discussion on basic plasma parameters in simple language with illustrations in some cases.",signatures:"Kashif Chaudhary, Auwal Mustapha Imam, Syed Zuhaib Haider Rizvi\nand Jalil Ali",downloadPdfUrl:"/chapter/pdf-download/57376",previewPdfUrl:"/chapter/pdf-preview/57376",authors:[{id:"176684",title:"Dr.",name:"Kashif Tufail",surname:"Chaudhary",slug:"kashif-tufail-chaudhary",fullName:"Kashif Tufail Chaudhary"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6408",title:"Novel Nanomaterials",subtitle:"Synthesis and Applications",isOpenForSubmission:!1,hash:"f3585d338d78e4d31c200d9991b03692",slug:"novel-nanomaterials-synthesis-and-applications",bookSignature:"George Z. Kyzas and Athanasios C. Mitropoulos",coverURL:"https://cdn.intechopen.com/books/images_new/6408.jpg",editedByType:"Edited by",editors:[{id:"152296",title:"Prof.",name:"George",surname:"Kyzas",slug:"george-kyzas",fullName:"George Kyzas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6215",title:"Graphene Materials",subtitle:"Advanced Applications",isOpenForSubmission:!1,hash:"3a921aba41351ab84fd7a9b4ea63914d",slug:"graphene-materials-advanced-applications",bookSignature:"George Z. Kyzas and Athanasios Ch. 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1. Introduction
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Endometriosis an estrogen dependent disease characterized by ectopic growth of endometrial glands and stroma outside of the uterine cavity. It is estimated that endometriosis may affect anywhere from 5 to 45% of all women [1]. Although retrograde menstruation has become the most widely accepted theory for the development of endometriosis [2], it cannot account for endometriosis in distant organs such as the lung and brain. Therefore, alternative explanations are sought.
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While the cause of endometriosis remains unknown, it most likely arises from a multifaceted origin involving the interaction of environment and genetics [3]. Among the different hypotheses advanced, a growing body of literature suggests that environmental factors including environmental toxicants may play a role in the pathophysiology of endometriosis. Lifestyle and medication use point to a role for environmental factors in endometriosis. While alcohol consumption and cigarette smoking have been associated with lower endometriosis risk [4], developmental exposure to diethylstilbestrol and early life exposure to soy formula as well as alcohol consumption in adulthood was linked with an increased risk of endometriosis [4, 5]. Support for an environmental toxicant influence on the development of endometriosis surged with the report of endometriosis in rhesus monkeys treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [6]. Evidence of estrogen mimicry, dysregulation of steroid signaling, and immune modulation by environmental toxicants such as the persistent organic pollutants including the polychlorinated biphenyls (PCBs), dioxins and dioxin like compounds, pesticides, plasticizers (phthalates and bisphenol A), and some metals has led some to hypothesize that human exposure to environmental toxicants may play an important role in reproductive health including endometriosis [3]. Although a recent systematic review and meta-analysis suggests a possible link between exposure to chlorinated organic chemicals and endometriosis [7], we postulate that the role of exposure to environmental toxicants in the pathophysiology of endometriosis remain uncertain.
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Potential associations between exposure to environmental toxicants and women with endometriosis have been equivocal with several finding positive associations [8, 9, 10] whereas others were unable to document an association [11, 12, 13]. Since our last review of the subject [14, 15, 16, 17] numerous studies have emerged suggesting a potential link between environmental toxicant exposure and endometriosis [7, 18]. Herein, we describe a systematic review and critical appraisal of the recent literature linking exposure to environmental toxicants and endometriosis using a modified weight-of-evidence approach to evaluate the strength of potential associations.
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2. Approach
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We conducted a systematic review of the literature between 2008 and present, to capture publications since our last review of the subject [14, 17]. An electronic search was performed using PubMed and web of science between October and November 2019. The following search terms were employed: endometriosis and environmental contaminants, environmental chemicals, environmental toxicants, endocrine disrupters, dioxins, polychlorinated biphenyls (PCBs), phthalates, bisphenol A, and metals. Inclusion criteria included biomonitoring, epidemiology studies reporting chemical concentrations in women with endometriosis compared to a reference population and associated risk. We also included articles describing experimental animal studies and in vitro experiments designed to explore the effect of chemical exposure on endometriotic lesion survival, growth, and to elucidate potential mechanisms relevant to human health. Review papers, meeting summaries, commentaries were excluded as were articles written in languages other than English. Article titles were downloaded into an Excel spreadsheet and duplicate titles excluded. Articles meeting inclusion and exclusion criteria were decided by review of article titles and abstracts by both authors. Disagreements were resolved through discussion. Articles meeting inclusion criteria were printed in full and read by both authors.
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3. Results
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Our electronic search of the literature revealed 67 articles from which four articles with duplicate titles were excluded (Figure 1). We further excluded six review articles. An additional seven articles were excluded because they either did not report chemical concentrations or associated risk for the development of endometriosis. Consequently, 50 articles were retained for full assessment. The largest group of articles addressed the association between exposure to chlorinated organic compounds including polychlorinated biphenyls (PCBs), dioxins, and dioxin-like compounds with relatively few studies exploring the link between pesticide exposure and endometriosis. Of the chemicals with comparatively short half-lives relative to the chlorinated organic compounds and potential to disrupt endocrine signaling pathways, several reports linking phthalate esters and bisphenol A with endometriosis were found in our search whereas relatively few studies involving perfluoroalkyl compounds and metals studies were found.
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Figure 1.
Flow diagram summarizing the process of candidate article title identification in our electronic literature searches (PubMed and Web of Science) conducted between January 2018 and February 2019, screening, and article selection vs. exclusion. The number of articles included vs. excluded and reasons for exclusion are indicated.
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3.1 Polychlorinated biphenyls (PCBs), dioxin and dioxin-like compounds
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PCBs are one of the most widely produced chemicals worldwide, with millions of pounds being produced globally over the last decade alone [19] for use a coolants in electrical transformers. With 209 possible congeners, PCB toxicity is dependent on chemical structure. For example, non-ortho or mono-ortho PCBs are far more toxic due to the loss of chlorine atoms on the 2,2′,6,6′ of the benzene rings [20]. Due to their diverse structures, PCBs share similar characteristics to estrogen, allowing them to have both agonistic and anti-estrogenic activity [21, 22]. PCBs have been known to disrupt several organs and tissue types throughout the human body; with particular damage to the liver, kidney, and the endocrine system [19]. Our search revealed several studies primarily focused on PCB exposure and endometriosis and additional studies that explored the link between dioxin and dioxin-like compounds and endometriosis (Table 1). Since these compounds are frequently found together in human tissues, we will discuss them together.
Increased risk of endometriosis for DL-PCB-118 (OR = 3.79; 95% CI, 1.61–8.91), NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10) were all significant in case versus controls.
PCB concentrations were higher in peritoneal fluid than serum. However, the total TEQ LOD and dioxin-like PCBs were not significantly different between women with endometriosis and the controls.
Several PCB congeners were associated with significantly lower risk (PCB 170 3rd quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.9) PCN196 (3rd quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7), PCB201 (2nd quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.8; and 3rd quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7) but not summed values (PCBs 170, 196, 201; OR = 1.3, CI 0.8–2.2) and estrogenic PCBs (OR = 1.1; 95% CI, 0.8–1.4).
Significant correlations for PCB concentrations within the three biological compartments omental versus peritoneal adipose tissue were found (p < 0.0001). 137.1 vs. 147.9 ng/g l.w. for sum of 6 NDL-PCB. Adipose vs. serum: WHO-TEQ2005 DL-PCB = 3.6 pg/g l.w., sum of 6 NDL-PCB = 81.1 ng/g l.w.
Dioxins and DL-PCBs were significantly higher in patients with deep infiltrating endometriosis; TCDD, PeCDD, PeCDF were the most significant p < 0.01 for each compound. PCB-126 (PCB-114 p < 0.05; PCB-156 p < 0.05; PCB-189 p = 0.04; PCB-126 p < 0.01).
DLC concentrations were marginally higher in patients with endometriosis (22.3±9.3 pg vs. 20.5±10.8 pg) and higher plasma levels of DLC were linked to a higher risk of endometriosis (aOR = 2.44; 95% CI 1.04–5.70; p = 0.04) adjusted for age. Moderate–severe endometriosis cases only (OR = 3.01; 95% CI 1.06–9.04; p = 0.03)
With the presence of the GSTP1 wild type genotype, medium-high levels of PCB 153, high levels of PCB 180 and total PCBS were significantly associated with endometriosis risk (OR = 6.00; 95% CI, 1.88–19.18 and OR = 9.08; 95% CI, 2.14–44.4, respectively).
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Table 1.
Summary of exposures and outcomes from biomonitoring studies designed to quantify the concentration of polychlorinated biphenyl congeners, dioxins, dioxin-like compounds (DLCs) and non-dioxin-like compounds (NDL) in women with endometriosis compared to healthy controls.
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In a pilot case–control study [24], involving 17 women (10 cases; 7 controls), superficial endometriosis was present in 90% of the cases. Of the 29 congeners measured in this study, both polychlorinated dibenzofurans (PCDFs) and dioxin-like (DL) -PCBs showed no significant difference between the case and control [24]. However, both were elevated in peritoneal fluid relative to the serum, with the reverse seen in polychlorinated dibenzo-p-dioxins (PCDDs) [24]. Both PCDDs and PCDFs in peritoneal fluid were significantly associated with an increased risk of endometriosis [24]. Although a potential association was found, the small sample size, the authors did not adjust for other factors such as age that have previously been shown to affect endometriosis risk. Hence, confidence in the findings from this pilot study is low. In contrast, results of a case–control study [23] of 158 Italian women (80 cases; 78 controls), revealed that both non-dioxin-like (NDL)-PCBs and DL-PCBs levels were significantly elevated in women with laparoscopically and histologically confirmed endometriosis. An increased risk of endometriosis was found for DL-PCBs (PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], and NDL-PCBs including PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10)). No significant associations were observed with respect to hexachlorobenzene (HCB) or to the sum of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs expressed as total toxic equivalent quotients (TEQs). PCB-101, PCB-156, and PCB-170 were all shown to be statistically elevated, with PCB-52, PCB-118, PCB-138, PCB-153, and PCB-180 showing a highly significant difference. All four stages and endometriosis implant localizations (peritoneal, deep, or ovarian) were analyzed, with no significant differences detected. However, the lack of adjustment for potential confounding and failure to account for multiple comparisons are important limitations of this study. IN another study [29], DLC concentrations were quantified in plasma samples using the dioxin-responsive chemical-activated luciferase expression bioassay (CALUX). Blood samples were collected prior to laparoscopic surgery from women with endometriosis (n = 96) and control patients with a normal pelvis (n = 106). A marginal increase in DLC compound concentrations in endometriosis patients relative to controls (22.3 ± 9.3 pg, versus 20.5 ± 10.8 pg CALUX-TEQ/g lipid) was reported [29]. After adjusting plasma concentrations for age only, an increased risk for endometriosis was demonstrated for high concentrations of DLC (OR = 2.44; 95% CI 1.04–5.70, p = 0.04) and when considering moderate to severe endometriosis (OR = 3.01; 95% CI 1.06–9.04, p = 0.03). While the authors adjusted for age, adjustment for BMI, parity, and breast feeding was not undertaken. Thus, these results although suggestive must be interpreted with caution.
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While several studies have provided evidence of a potential link significant associations between women with endometriosis and PCB levels could not be demonstrated by other investigators [25, 28, 31]. No significant association between PCBs and endometriosis risk was found in a study of 789 patients (251 cases; 538 controls); with 20 PCB congers measured in serum from surgically confirmed cases [25]. While the odds ratios (ORs) for several PCB congeners did show significant levels above and below the null; however, there was no specific pattern associated with endometriosis risk. Several PCBs were quantified in the serum of 473 women in an operative cohort (190 cases; 283 controls) and 127 patients from a general population cohort (14 cases; 113 controls), using omental fat in the operative cohort and serum in both [31]. Results were adjusted for confounding variables such as age, BMI, breast-feeding, cotinine, and lipids. Among the 35 PCB congers analyzed, geometric mean serum PCB levels were found to be inversely related in terms of risk in the operative cohort, with the opposite seen in the population cohort [31]. A similar relationship can be seen in omental fat, with sum PCB levels showing significantly higher levels in the non-endometriosis patients relative to the controls. Limitations of this study include the small number of women with endometriosis in the case population (only 11% of women had endometriosis), possible bias through the use of telephone directories, and use of controls without surgical confirmation of absence of disease suggest that results be interpreted with caution. The relationship between exposure to DLCs and deep infiltrating endometriosis (DIE) was explored in a case–control study of 30 cases and 30 controls [28]. Disease status was determined by clinical examination, magnetic resonance imaging (MRI), and transvaginal ultrasonography (TVUS), whereas the control population underwent laparoscopic surgery for adnexal benign gynecological disease. DLCs were analyzed omentum adipose tissue in both groups. The results suggest a significant increase of both dioxins and PCBs relative to the control, with the most toxic forms showing a significant difference (2,3,7,8-TCDD and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]; p < 0.01) [28]. Furthermore, 2,3,4,7,8-PeCDF was also significantly higher and four of the most toxic PCB congeners (PCB 144, 156, 189, 126) had toxic equivalence values (TEQ) that were statistically higher in DIE patients [28]. However, no differences were seen when the data were adjusted for age, breast feeding, and BMI. Limitations of this study include small sample size, and homogeneity of the sample population [28].
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A biomonitoring study conducted in France [26], measured the concentrations of PCBs in serum, peritoneal and omental adipose tissue of 113 adult French women with deep infiltrating endometriosis (DIE) (45 controls, 68 cases). There was a significant difference between omental versus peritoneal adipose tissue PCB concentrations (p < 0.0001). Similar trends were seen is peritoneal adipose tissue versus serum levels, with PCBs showing the highest level of significance in terms of concentration differences.
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Potential gene–environment interaction among women with endometriosis was explored [30]. Specifically, the relationship between glutathione transferase (GST) gene polymorphisms PCB concentrations in a study of 343 Italian women (181 cases; 162 controls). Ability glutathione enzymes to regulate oxidative free radicals and thus oxidative stress and therefore genetic polymorphisms may influence tissue capacity to manage the damaging effects oxidative stress, in turn influencing disease susceptibility. No significant difference in genotype distribution (GSTM1, GSTA1, and GSTP1) between case and control patients could be elicited [30]. However, the GSTP1 wild-type with medium-high blood levels of PCB153, high levels of PCB180, or total PCB levels, showed a significant increase in potential risk, while GSTT1 null was negatively associated with the disease [30]. The potential association between five microsatellites and 28 single nucleotide polymorphisms among 10 dioxin detoxification genes (aryl hydrocarbon receptor (AhR), AHRR, ARNT, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) was examined in 242 women (100 case; 143 control) from Japan [32]. Accounting for disease stages I-IV, BMI, and smoking, no significant association was seen between the polymorphisms and the contribution to the etiology of endometriosis. Taken together, these data suggest that genetic polymorphisms in detoxification enzymes do not modulate endometriosis risk.
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Establishing a link between exposure to environmental toxicants and endometriosis using epidemiology and biomonitoring is difficult owing to challenges in diagnosis of endometriosis [33], lengthy diagnostic delays [34], and high prevalence of endometriosis in asymptomatic women [1] and thus the potential for misclassification error is high. Therefore, animal studies have been employed to better understand the potential hazard posed between toxicant exposure and endometriosis. Developmental exposure of mice to TCDD induced a progesterone-resistant phenotype in adult animals that persisted across generations [35]. Results of this study suggest that TCDD induced activation of the aryl hydrocarbon signaling pathway induces dysregulation of expression of tissue remodeling enzymes, and contributes to the inflammatory responses, cell migration, and proliferation seen in endometriosis patients. These data are supported by prior animal studies demonstrating PCB and dioxin effects in animal models of endometriosis [36, 37, 38].
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Tissue culture studies have been employed to elucidate potentially important toxicant regulated mechanisms. PCBs have been linked to an increased estradiol synthesis and creating an inflammatory milieu through the production of interleukin (IL)-6 and IL-8 [39]. Primary cultures of endometrial stromal cells (ESCs) were treated with both DL-PCBs and NDL-PCBs. Dioxin-like CB126 treatment increased 17β-estradiol (E2) biosynthesis in a dose dependent manner. CB126 exposure also increased 17β-hydroxysteroid dehydrogenase 7 (HSD17B7) as well as decreased methylation of the HSD17B7 promoter leading to an increase in expression. Inflammatory markers were also elevated in cultured endometrial stromal cells. Increased inflammation and E2 synthesis were demonstrated in a mouse model of endometriosis [39]. Although PCB has shown to increase E2 biosynthesis, combining 17β-Estradiol with TCDD showed a synergistic effect and induces M2 activation with macrophages co-cultured with ESCs. STAT3 and P38 phosphorylation in macrophages were also increased differentiation of M2 macrophages, leading to an inflammatory milieu [40]. Several studies also analyzed the impact of TCDD exposure on progesterone-dependent mechanisms. TCDD was found to induce cannabinoid receptor type 1 CB1-R mRNA expression in endometrial stromal cells and steroid-induced expression of the gene was inhibited. Through the use of tissue obtained from women with and without endometriosis, TCDD treatment-induced dysregulation of cannabinoid signaling, immune cell migration into the endometrium during embryo uterine attachment [41] and thus we propose could be an important mechanism in the pathophysiology of endometriosis. PCB was also seen to activate endogenous aryl hydrocarbon receptor (AhR) signaling pathway in immortalized human telomerase reverse transcriptase (hTERT) endometrial epithelial cell (hTERT-EEC), specific to time, concentration, and congener. The changes induced were modulated by changes in estrogen levels, in turn increasing cell migration by hTERT-EEC. Proteomic analysis also identified cell stress responses and metabolism markers (such as heat shock proteins (HSP) 27 and HSP 70) [42]. These proteins are both critical markers for the regulation of apoptosis and cellular stress response pathways. In another study [43] primary cultures of ESCs from both case and control patients showed that PCB-104 exposure affects cell migration, invasion and resultant gene expression. Treatments induced a significant increase in cell migration and invasion of ESCs. Enzyme-linked immunosorbent assays showed a time and dose dependent increase in matrix metalloproteinase 3 (MMP-3) and MMP-10 protein in ESCs, whereas MMP-2, MMP-9, TIMP-2, E-cadherin, Snail and Slug did not. MMP-3 contributes to the breakdown of the extracellular matrix and promotes tissue remodeling and migration [43]. The results from this study suggest that PCB-104 increased migration and invasion of ESCs through increasing MMP-3 and MMP-10 [43]. Taken together, results from tissue culture studies elucidate PCB and dioxin induced dysregulation of mechanisms potentially important in the pathophysiology of endometriosis.
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In summary, several studies demonstrated a potential association between exposure to PCBs, dioxins, and dioxin-like compounds and increased risk of endometriosis; however, important study limitations decrease confidence in these study findings. Moreover, several studies were unable to evoke evidence of an association between exposure to these toxicants. While, animal studies are few, results from these studies provide evidence of biological plausibility. Results of tissue culture studies also provide evidence that PCBs and dioxins adversely affect mechanistic pathways important in the pathophysiology of endometriosis although the effective concentrations exceed human exposure. Consequently, we suggest that there is weak evidence linking exposure to PCBs and dioxin and DL-PCBs in the pathophysiology of endometriosis.
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3.2 Pesticides
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Chlorinated organic pesticides (COPs) resist degradation in the environment, are lipophilic and thus bioaccumulate in adipose tissues, and concentrations are biomagnified with increasing trophic level. Moreover, COPs are able to travel long distances and remain stable for several decades in the environment, and thus widespread human exposure to these chemicals has frequently been documented. Despite widespread human exposure, the relationship between pesticides and endometriosis risk in general are equivocal.
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The concentrations of six COP levels were measured with gas chromatography and electron-capture, in blood samples of laparoscopically confirmed cases of endometriosis [44]. Results showed that aromatic fungicides had a five-fold increase in risk (aOR = 5.3; 95% CI, 1.2–23.6) when comparing the highest and lowest tertile after adjusting for smoking and serum lipids [44]. Chlordane (t-nonachlor) (aOR = 4.6; 95% CI, 0.5–41.6) and HCB (aOR = 6.4; 95% CI, 1.0–42.8) showed a similar trend [44]. Aldrin, β-hexachlorocyclohexane (β-BHC) and mirex also had increased ORs; however, few women had concentrations above the limit of detection preventing further analysis. Two other studies yielded similar results. Specifically, hexachlorocyclohexane (HCH) was associated with an increased risk of endometriosis in a large study with 248 surgically confirmed endometriosis cases and 538 controls [45]. β-HCH concentrations were significantly elevated in the serum (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0–2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8–2.4), as well as for mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0–2.2). The results were adjusted for participant age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Although trends were seen throughout multiple forms of endometriosis, the strongest association was seen in women with ovarian endometriosis. Similarly, γ-hexachlorocyclohexane (γ-HCH) had a significant association with endometriosis risk (adjusted OR (AOR) for age, body mass index, breast-feeding conditional on parity, cotinine, and lipids = 1.27; 95% CI: 1.01–1.59) [31]. Although these studies provide evidence for a link between exposure to different pesticides and increased risk of endometriosis, there are several limitations to note. In particular, while the authors adjusted their data for some potential confounding variables none appeared to adjust for BMI. Moreover, since multiple pesticides were quantified in each study, correction for multiple comparisons would add confidence to the findings and exclude the potential for type I error. Furthermore, the lack of a dose–response relationship [45] suggests that chance discovery cannot be excluded.
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We found no recent animal studies and only one in vitro study was found. HCB treatment enhanced MMP-2 and MMP-9 activities in human endometrial stromal cell line T-HESC, primary cultures of Human Uterine Fibroblast (HUF), and ESCs [46]. Specifically, MMP-2 was only elevated in ESCs, whereas MMP-9 was elevated in all models. An increase in COX-2 and prostaglandin receptor-4 expression, prostaglandin E2 secretion and the c-Src kinase activation in T-HESC was also seen after HCB exposure. The results suggest that HCB may promote inflammation and invasion parameters through regulation of the AhR pathway.
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In summary, the epidemiological and biomonitoring studies suggest a potential association between exposure to chlorinated organic pesticides and increased risk of endometriosis; however, study limitations cannot exclude chance discovery owing to multiple comparisons, failure to adequately adjust for important confounders and lack of a dose–response relationship all weaken confidence in the link between COP exposure and endometriosis risk. A single tissue culture animal experiment conducted within the search window suggests that it is biologically plausible for COPs to promote endometriosis risk. Consequently, we suggest weak evidence linking exposure to COPs and endometriosis.
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3.3 Perfluoroalkyl and polyfluoroalkyl substances
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Perfluoroalkyl substances are a rather unique group of compounds due to their seemingly harmless properties. However, over the last decade, perfluoroalkyl and polyfluoroalkyl substances have been detected in blood and urine across the globe [47, 48]. Compromised of carbon-fluorine atoms, this extremely strong bond forms stable compounds that are used in clothing, cookware, carpets, and other common household items. Exposure to these compounds has been linked to adverse effects on metabolism, immune function, and fertility [49, 50, 51].
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In a case–control study [27], nine perfluorochemicals (PFCs) were measured in the blood of study participants by liquid chromatography–tandem mass spectrometry. Surgical visualization was used to confirm endometriosis in the operative population and MRI was used to confirm the absence of endometriosis in the control population. Both perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17–3.06]) and perfluorononanoic acid (PFNA) (2.20 [1.02–4.75]) were seen to be associated with endometriosis risk, where results were only moderately changed when adjusted for fecundity [27]. Patients with more severe stages of endometriosis (Stages III and IV) showed a higher concentration of perfluorooctane sulfonic acid (1.86 [1.05–3.30]) and PFOA (2.58 [1.18–5.64]) in their blood compared to controls [27]. Although this study shows a significant association between PFC exposure with an apparent dose response, there are a number of limitations to consider. First assignments of healthy study participants to the control population using MRI alone to exclude asymptomatic endometriosis cannot exclude women with endometriosis. Undiagnosed endometriosis was found in 45.3% of asymptomatic women undergoing laparoscopies for benign conditions [1] and thus the potential for misclassification error in this study weakens confidence in the purported association. Finally, circulating concentration of PFCs from the NHANES (2003–2006) study was compared in 753 women with self-reported diagnosis compared to healthy women without a diagnosis of endometriosis [52]. Results from this study showed that PFNA, PFOA, and perfluorooctane sulfonate (PFOS) were significantly higher among women with endometriosis compared to the control population. Women in the referent population of this study were significantly younger, non-Hispanic white, had more than one menstrual period in the last year and reported to be pregnant at the time of the exam. Furthermore, use of self-reported diagnosis of endometriosis may introduce group assignment bias and thus, these data must be interpreted with caution.
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The data linking exposure to Perfluoroalkyl substances and endometriosis are limited to the results of two biomonitoring studies. Although the results suggest that women with endometriosis have exposure to Perfluoroalkyl substances, any potential association with endometriosis is weak owing to limitations of these studies and absence of experimental animal studies or mechanistic experiments.
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3.4 Bisphenol A (BPA)
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A monomeric compound, bisphenol A (BPA) is used to polymerize plastics and can be found in common household items such as toilet paper, water bottles, the lining of tin cans, cash register receipts, dental sealants, and building supplies [53]. With over a million tons of BPA being used in the United States alone, BPA has become ubiquitous in the environment leading to widespread human exposure. BPA is able to bind to both estrogen receptors (Esr1 and Esr2), activate the estrogen signaling cascade and thus is considered a xenoestrogen [54]. Estrogenic capacity has led some to postulate that BPA exposure may play a role in the pathophysiology of endometriosis (Table 2).
Urinary BPA levels were found in all analyzed samples; with a statistically significant difference between patients and controls. Urinary BPA concentrations were significantly greater (p = 0.001) in women with endometriosis compared to the control group.
No statistically significant association between total urinary BPA concentrations and endometriosis overall. However, significant results were seen in urine in relation to non-ovarian pelvic endometriosis (2nd quartile vs. lowest quartile: OR = 3.0; 95% CI: 1.2–7.3 and 3rd vs. lowest quartile: OR = 3.0; 95% CI: 1.1–7.6), but not ovarian endometriosis.
BPA was found in 51.7% and BPB was found in sera 27.6% but either could not be detected in all the control cases. Suggests an association between at least one of the compound endometriosis risk.
No significant (p = 0.24) association of endometriosis with urinary BPA concentration.
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Table 2.
Summary of exposures and outcomes in epidemiological studies designed to investigate the association between Bisphenol A (BPA) exposure and endometriosis.
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A population-based case–control study [56], analyzed the urine from 143 women with confirmed or suspected endometriosis (cases) and 287 healthy controls. Urinary creatinine concentrations, age, reference year, as well as both ovarian and non-ovarian pelvic endometriosis were taken into account. Overall, the urinary BPA concentrations in cases did not differ from the control group. However, unconditional logistic regression analysis revealed that the second versus lowest quartile and third versus lowest quartile had increased adjusted odds ratio (aOR 3.0; 95% CI: 1.2–7.3 and aOR 3.0; 95% CI: 1.1–7.6) for higher BPA concentrations in women with non-ovarian pelvic endometriosis; however, there was no association between urine BPA concentrations and ovarian endometriosis. Moreover, there was no relationship between the highest urine concentrations of BPA and endometriosis overall as well as for non-ovarian pelvic endometriosis and ovarian endometriosis. Furthermore, the lack of a dose–response relationship with increasing urine concentrations of BPA weakens confidence in the potential link between BPA exposure and endometriosis risk.
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Results of biomonitoring studies revealed that mean BPA concentrations in the plasma of infertile women with endometriosis (n = 11), polycystic ovarian syndrome (PCOS, n = 31) and PCOS plus endometriosis (n = 3) combined (4.66 ± 3.52, 95% CI; 3.60–5.72 ng/ml) were significantly greater than in a control population (n = 34) of healthy fertile women (2.64 ± 3.99, 95% CI; 1.24–4.03 ng/ml) [59]. In women who reported a diagnosis of endometriosis, the mean ± (SD) concentration of BPA was 4.59 ± 1.22 ng/ml (range < LOQ – 5.31 ng/ml). Moreover, BPA concentrations were quantifiable in only 3% of study participants and comparisons with the fertile controls was not reported. Given the ubiquitous nature of BPA, the low detection frequency in this study is rather surprising and thus we interpret these findings with caution. The small sample size, self-reported diagnosis of endometriosis and associated potential for misclassification error are important limitations of this study. Results of a much larger cross-sectional study of 166 Japanese women [58], showed no significant difference in BPA levels in the urine. BPA concentrations were non-significantly (p = 0.24) greater in women with endometriosis stage 0–I (median = 0.74 μg/g after adjusting to creatinine levels), whereas women with stages II-IV endometriosis had a median concentration of 0.93 μg/g creatinine [58]. BPA levels measured in the sera from healthy fertile (n = 11) and endometriotic women (n = 58) found that both BPA and bisphenol B (BPB) levels were detectable in 51.7% and 27.6% of cases, respectively whereas the control patients showed a complete absence of both compounds [57]. Recently, urinary concentrations of BPA were significantly greater in women (n = 68) with endometriosis (1.17–12.68 pg/μl) compared to a control population (n = 60) (1.28–2.35 pg/μl) [55]. Finally, BPA has a short half-life and the measures in women with a diagnosis of endometriosis are temporally disconnected from the onset of disease which may have originated years earlier in time. The interval between onset of symptoms and diagnosis ranges from 6 to 12 years [34] and thus exposure measurements made after diagnosis are difficult to link with the development of endometriosis. Therefore, reverse causation cannot be excluded as a potential explanation for differences in circulating concentrations of the toxicants measured.
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In an animal study [60], BPA and bisphenol AF (BPAF) affected endometriosis lesion development in ovariectomized and hormonally intact mice specific to dose and hormonal status of the host mouse. Minced uterine tissue was injected into the peritoneal cavity of host mice. In this study, BPA treatment disrupted ovarian steroidogenic pathways resulting in lower progesterone levels and higher atretic oocyte numbers [60]. BPAF and BPA had higher epithelial proliferation scores, although this was only significant in the highest dose of 900 ppm. Both compounds mimicked estrogen, with BPAF having a stronger effect than estrogen [60]. Taken together, these data suggest that BPA and related compounds can affect mechanisms important in the pathophysiology of endometriosis. However, the concentrations of BPA needed to achieve these effects are higher than human exposure and thus are unlikely to be relevant at the concentrations of BPA measured in the general human population in contemporary studies.
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Results of a tissue culture experiments demonstrated that BPA treatment arrested human ESCs at the G2/M phase of the cell cycle, allowing for cell migration. Progesterone amplifying receptors such as insulin growth factor binding protein 1 and prolactin were also increased in response to BPA treatment [61]. These results suggest that BPA exposure could modulate endometrial stromal cells function; however, the effective concentrations exceed human exposure. Consequently, ambiguous study results from biomonitoring studies and lack of animal studies suggests a lack of association between BPA exposure and risk of endometriosis.
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3.5 Phthalate esters
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Phthalate esters are used as a softener in polyvinyl chloride plastics to make plastics flexible and can be found in products such as cosmetics, building materials, and in medical equipment such as intravenous bags, tubing and rubber stoppers in syringes and blood collection tubes. Phthalates leach from finished products leading to ubiquitous human exposure [62, 63]. Exposure to phthalate esters has been linked with decreased circulating testosterone [64] and animal experiments have shown that phthalates are competitive antagonists of the androgen receptor that displace testosterone from the receptor increasing its availability for conversion to estrogens via aromatase [65]. Therefore, it is postulated that exposure to phthalates could be associated with increased risk of endometriosis (Table 3).
Significantly higher plasma concentrations of MBzP (95% CI; 11.69–28.12 versus 3.34–8.10), BPA (95% CI; 3.60–5.72 versus 1.24–4.03), and MEHHP (95% CI; 5.10–8.43 versus 0.58–2.85).
Positive associations for MBP (OR = 1.36; 95% CI, 0.77–2.41) for the highest versus lowest three quartiles, and inverse associations for MEHP in relation to endometriosis (OR = 0.44; 95% CI, 0.19–1.02)
Greater urinary concentrations of MBzP and MEP in the urine of women with endometriosis compared to controls. Strong inverse association between urinary MEHP and endometriosis risk (aOR 0.3, 95% CI: 0.1–0.7).
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Table 3.
Summary of exposures and outcomes in epidemiological studies designed to investigate the association between phthalate exposure and endometriosis.
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A large case–control study [67], examined 626 women (495 cases; 131 controls) from 14 clinical centers. Study participants in both groups had a laparoscopy or a pelvic MRI to diagnose the presence of endometriosis. Among the 14 phthalate metabolites, mono-n-butyl phthalate, mono-[(2-carboxymethyl) hexyl] phthalate, mono (2-ethyl-5-carboxyphentyl) phthalate, mono (2-ethylhexyl) phthalate, mono (2-ethyl-5-hydroxyhexyl) phthalate, and mono (2-ethyl-5-oxohexyl), all showed two-fold significant increase in the odds of diagnosis. Results were adjusted for age, BMI, and creatinine. Depending on the method of diagnosis, monooctyl phthalate was restricted to surgical diagnosis of endometriosis with histological confirmation, whereas mono (2-ethylhexyl) phthalate was restricted to surgical diagnosis alone. However potential limitations may arise through adding concentrations as mECPP, mEHHP, mEOHP where all are metabolites of DEHP that were elevated in the operative cohort. Yet when summing DEHP metabolites (mECPP, mCMHP, mEHHP, mEOHP, and mEHP), there is a higher odds of endometriosis in the control population cohort. A further limitation is the lack of adjustment for multiple comparisons and thus chance discovery cannot be excluded. A large study from the National Health and Nutrition Examination Survey (NHANES, 1999–2004), examined phthalate levels in 1227 women, with a self-reported history of endometriosis and uterine leiomyomata. MEHP, monobutyl phthalate (MBP), monoethyl phthalate (MEP), and MBzP levels were measured in patients with each disease as well as patients that reported both [69]. Comparing the highest versus lowest three quartiles of urinary phthalate levels, MBP had an OR of 1.36 (95% CI, 0.77–2.41), MEHP was 0.44 (95% CI, 0.19–1.02), with no association for MEP and MBzP in endometriosis patients. Significantly higher plasma concentration of DBP which is broken down into MBP was also seen [69]. However, the use of self-reported cases may be unreliable. Contrary to the NHANES study, an increased endometriosis risk with an increase in urinary MBzP and MEP was described although the results were not significant [71]. Moreover, an inverse relationship between endometriosis risk and urinary MEHP was found (OR = 0.3; 95% CI = 0.1–0.7) and an inverse relationship was also suggested for DEHP, MEHHP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and ΣDEHP. Therefore, a compelling link between phthalate exposure and endometriosis has not been established.
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Results of several biomonitoring studies have documented higher concentrations of phthalate metabolites in the urine of women with endometriosis compared to a reference population. Plasma concentrations of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were recently quantified by gas chromatography–mass spectrometry in infertile women with endometriosis (n = 11), polycystic ovarian syndrome (PCOS, n = 31) and PCOS plus endometriosis (n = 3) and 34 fertile women without evidence of gynecological disorders [59]. Overall, the mean (± SD) concentrations (ng/ml) of MBzP (19.9 ± 27.3 95% CI;11.69–28.12) and MEHHP (6.76 ± 5.54, 95% CI; 5.10–8.43) were significantly higher in infertile women compared to fertile women (5.72 ± 6.82, 95% CI; 3.34–8.10 and 1.71 ± 3.24, 0.58–2.85; respectively), whereas no differences were detected between groups for MMP and MEHP. The mean concentrations of MBzP and MEHHP in women with endometriosis were 40.9 ± 51.4 (range < LOQ – 116.5) and 5.43 ± 5.53 ng/ml (range < LOQ – 14.76), respectively. However, only 4–5% of women with endometriosis had concentrations of MBzP and MEHHP above the LOQ . Study participants were assigned to groups based upon self-reports of gynecological diagnoses which is open to misclassification error. In addition, the small sample size overall together with the limited number of study participants with quantifiable concentrations of phthalates are important limitations of this study.
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Recently, differences in serum DEHP concentrations were found between women with endometriosis and control patients using high-performance liquid chromatography [66]. The mean ± SD concentration of DEHP in cases (n = 50) was 65.3 ± 21.7 ng/ml, whereas it was undetectable in the controls. Among the four stages of the disease, women with endometriosis showed a linear increase in DEHP concentration with more advanced stages, although the sample size for stage I was n = 1. Age groups did not impact DEHP serum levels. Controversy remains, as DEHP is broken down by glutathione S-transferase and P450 enzyme, which has been reported to be compromised in endometriosis patients [72]. This may explain the difference in serum concentration, as the control patients are able to metabolize DEHP into metabolites which were not recorded. A further weakness of this study is the measurement of DEHP in the serum rather than metabolites in either the serum or urine and thus the potential for sample contamination cannot be discounted.
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A group from Taiwan investigated the association between GSTM1 polymorphisms and phthalates in adenomyosis, leiomyoma and endometriosis [68]. Although no relationship between the gene and the disease was found, there was an increase in urinary mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine, p < 0.05) among the 28 women with endometriosis relative to the 29 controls. In a subsequent study [70], the potential relationship between polymorphisms of CYP17A1 and phthalate exposure was explored in women with leiomyoma (fibroids, n = 36), endometriosis or adenomyosis (n = 44) and healthy controls (n = 69). However, only a marginally increased level of urinary MEHP was found in patients with endometriosis or adenomyosis [70].
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Our search failed to identify any experimental animal studies and only two mechanistic studies were located. MMP-2 and 9 activities, cellular invasiveness, Erk phosphorylation, and p21-activated kinase 4 expression (PAK4) were increased in endometrial stromal cell cultures exposed to DEHP [73]. All five significantly elevated markers play a role in cellular division, actin cytoskeletal dynamics, motility, cell survival, and immune defense [73, 74]. Another study found that DEHP treatment increased ESC reactive oxygen species (ROS) generation and decreased expression of superoxide dismutase (SOD), glutathione peroxidase (GPX), heme oxygenase (HO), and catalase (CAT). p-ERK/p-p38 and NF-κB were also increased [75]. This provides a potential explanation for the decreased expression of antioxidant enzymes and increased ROS. Lastly, Esr1 expression was also increase proportional to dose [75].
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In summary, while several studies revealed higher phthalate esters concentrations in women with endometriosis compared to controls the results of epidemiological studies remain equivocal. Moreover, the short half-life of 5–6 h for these chemicals suggests that higher concentrations detected in women with endometriosis compared to controls may be a consequence of the disease rather than a causal factor and thus reverse causation cannot be excluded. While in vitro studies suggest that phthalate esters can adversely affect mechanisms relevant to the pathophysiology of endometriosis, the effective concentrations are beyond human exposure and thus are unlikely to be clinically important.
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3.6 Metals
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Trace metals are nearly impossible to avoid in one’s lifetime, as they are found both naturally in our bodies and are produced during industrial processes. Exposure to metals has been reported to interfere with cell proliferation, migration, cell degeneration, oxidative stress, and apoptosis, nearly all of which are properties of endometriosis [76]. Therefore, a link between circulating concentrations of metals and endometriosis has been explored by several groups.
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A positive relationship between lead and endometriosis (adjusted OR = 2.59, 95% CI = 1.11–6.06) was found in Asian women whereas zinc levels were inversely associated with the disease (adjusted OR = 0.39, 95% CI = 0.18–0.88) [77]. While cadmium (Cd) levels were greater in women with endometriosis, the adjusted odds ratio was not significant [77]. Furthermore, no significant relationship was found between 20 trace elements quantified in the urine and three in blood [76]. Cases were surgically confirmed, whereas the controls were confirmed for the absence of endometriosis through MRI. Contrary to the findings by [24], Cd was inversely related to endometriosis risk, while urinary chromium and copper were marginally associated with endometriosis (aOR = 1.97; 95% CI: 1.21–3.19; aOR = 2.66; 95% CI: 1.26–5.64) [76]. Comparisons for each of the metals increase the probability of chance discovery and thus any association is considered suspect.
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Our search of the literature failed to reveal any recent animal studies; however, a tissue culture study revealed that Cd treatment-induced higher ESC proliferation (p = 0.02) in cultures derived from eutopic endometrium of women with endometriosis compared to controls [78]. Although the mechanism was not identified, it is suggested that Cd at 10−5 M is the toxic threshold for ESCs [78], a concentration that is orders of magnitude above typical human exposure.
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In summary, biomonitoring studies offer weak support for a potential link between metals exposure and endometriosis. Moreover, results from a tissue culture experiment suggest that Cd can adversely affect ESC proliferation but only at concentrations far in excess of human exposure. Consequently, we consider the evidence of a link between exposure to metals and risk of endometriosis to be speculative at best.
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4. Future directions
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The current literature fails to provide compelling evidence for an association between exposure to environmental toxicants and endometriosis risk. Although current evidence is weak, involvement of environmental toxicants in the pathophysiology of endometriosis cannot be excluded. However, we propose that establishing a link between exposure to environmental toxicants and endometriosis is particularly challenging. Endometriosis is a heterogeneous disease in which peritoneal and ovarian endometriomas may arise by mechanisms that differ from DIE [79] and thus environmental interactions may be different from other forms of the disease.
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Absence of diagnostic tools such as a blood test for endometriosis together with normalization of pelvic pain and use of oral contraceptives among other factors leads to lengthy delays in diagnosis. Importantly, the interval between the onset and symptoms and definitive diagnosis of disease can be lengthy varying between 6 and 12 years [34]. Thus, there is a temporal disconnection between collection of biological samples for analysis and the onset of disease. Hence, the use of case–control studies may not permit convincing evidence of an association and the potential for reverse causation cannot be excluded.
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Identification of appropriate control groups poses an additional challenge since the prevalence of endometriosis in asymptomatic women can be high [1]. Furthermore, the hallmarks of endometriosis include chronic pelvic pain and infertility. Women dealing with chronic pain and or infertility may adopt activities or behaviors to reduce their pain or improve their chances of conceiving that diverge from the healthy fertile population and thus their exposures may be a function of disease status rather than factors contributing to the pathophysiology of endometriosis. Consequently, in the absence of clinical tools to diagnosis endometriosis, the most appropriate control group in the future may be symptomatic women undergoing laparoscopy with careful inspection of the pelvic cavity to exclude the presence of endometriosis, even though this step is admittedly imperfect [80].
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Epidemiological studies that adjust for potential confounders (e.g. age, BMI, parity, breast feeding, cigarette smoking, and alcohol consumption) and account for multiple comparisons could prove valuable in elucidating the role of exposure to environmental toxicants in the pathophysiology of endometriosis. Finally, it is unlikely that any group of women are exposed to a singly chemical or group of chemicals and thus quantification of chemicals from different chemical groups in a single study with an appropriate control, control for confounds and correction for multiple comparisons could prove informative.
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In the absences of robust epidemiological data experimental animal studies take on greater importance for establishing biological plausibility of a potential association. In general, there is a paucity of literature addressing the potential hazards of environmental toxicants in the survival and growth of endometriotic implants in animal models of endometriosis. While spontaneous endometriosis is predominately limited to humans and some non-human primates, animal xenotransplant models using dispersed cells from ectopic implants in women with endometriosis can provide valuable insight into potential chemical hazards relevant to endometriosis and mechanisms. However, dose levels used should include a concentration representative of human exposure. Similarly, tissue culture studies are essential for mechanistic insight; however, we propose that test concentrations should cover a range of doses that include concentrations below and representative of human exposure as well as high doses through to toxic levels.
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5. Summary and conclusions
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While in general, the epidemiological studies are judged to provide weak evidence of an association between exposure to environmental toxicants and endometriosis, a potential link cannot be excluded. Animal and cell culture models suggest biologically plausible mechanisms between the environmental toxicant exposures and endometriosis risk; however, the effective concentrations exceed human exposure levels. Consequently, we conclude that a causal relationship between exposure to any environmental toxicant and endometriosis does not currently exist, but the evidence does not allow us to exclude a potential link.
\n
\n\n',keywords:"endometriosis, endocrine disrupters, phthalates, bisphenol A, dioxin, estrogenic",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/70843.pdf",chapterXML:"https://mts.intechopen.com/source/xml/70843.xml",downloadPdfUrl:"/chapter/pdf-download/70843",previewPdfUrl:"/chapter/pdf-preview/70843",totalDownloads:765,totalViews:0,totalCrossrefCites:1,totalDimensionsCites:1,totalAltmetricsMentions:14,impactScore:1,impactScorePercentile:52,impactScoreQuartile:3,hasAltmetrics:1,dateSubmitted:"October 22nd 2019",dateReviewed:"December 26th 2019",datePrePublished:"February 3rd 2020",datePublished:"January 14th 2021",dateFinished:"January 17th 2020",readingETA:"0",abstract:"Endometriosis is widely acknowledged to be an estrogen dependent disease or unknown etiology. Recognition that environmental toxicants can bind with and activate the estrogen receptor, dysregulate steroid metabolism and, in some cases, act as anti-androgenic substances (phthalate esters) has led to proposal that exposure to environmental toxicants are associated with increased risk of endometriosis. Since our last review of the subject in 2008, the literature has expanded with several epidemiological and biomonitoring studies suggesting a potential association, whereas others have been unable to demonstrate a link between exposure and enhanced risk. Therefore, we carried out a systematic review and critical appraisal of the literature published over the past decade (2009–2019). The majority of studies found dealt with exposure to polychlorinated biphenyls (PCBs), dioxins, dioxin-like and non-dioxin-like compounds, bisphenol A and phthalate esters. Several studies suggest a potential association between exposure to environmental toxicants; however, important weaknesses in study design, methodology, and analysis together with many contradictory studies weaken confidence in these associations. Consequently, we conclude that despite a growing literature, evidence for an association between exposure to environmental toxicants and risk of endometriosis remains weak.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/70843",risUrl:"/chapter/ris/70843",book:{id:"9785",slug:"endometriosis"},signatures:"Shay M. Freger and Warren G. Foster",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Approach",level:"1"},{id:"sec_3",title:"3. Results",level:"1"},{id:"sec_3_2",title:"3.1 Polychlorinated biphenyls (PCBs), dioxin and dioxin-like compounds",level:"2"},{id:"sec_4_2",title:"3.2 Pesticides",level:"2"},{id:"sec_5_2",title:"3.3 Perfluoroalkyl and polyfluoroalkyl substances",level:"2"},{id:"sec_6_2",title:"3.4 Bisphenol A (BPA)",level:"2"},{id:"sec_7_2",title:"3.5 Phthalate esters",level:"2"},{id:"sec_8_2",title:"3.6 Metals",level:"2"},{id:"sec_10",title:"4. Future directions",level:"1"},{id:"sec_11",title:"5. Summary and conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'\nRawson JM. Prevalence of endometriosis in asymptomatic women. The Journal of Reproductive Medicine. 1991;36:513-515\n'},{id:"B2",body:'\nSampson J. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. American Journal of Obstetrics and Gynecology. 1927;14:422-469\n'},{id:"B3",body:'\nMatta K, Ploteau S, Coumoul X, Koual M, Le Bizec B, Antignac JP. et al. Associations between exposure to organochlorine chemicals and endometriosis in experimental studies: A systematic review protocol. Environment International. 2019;124:400-407\n'},{id:"B4",body:'\nMissmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. American Journal of Epidemiology. 2004;160:784-796\n'},{id:"B5",body:'\nUpson K, Sathyanarayana S, Scholes D, Holt VL. Early-life factors and endometriosis risk. Fertility and Sterility. 2015;104:964.e965-971.e965\n'},{id:"B6",body:'\nRier SE, Martin DC, Bowman RE, Dmowski WP, Becker JL. Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to tetrachlorodibenzo-p-dioxin. Fundamental and Applied Toxicology. 1993;21:433-441\n'},{id:"B7",body:'\nCano-Sancho G, Ploteau S, Matta K, Adoamnei E, Louis GB, Mendiola J, et al. Human epidemiological evidence about the associations between exposure to organochlorine chemicals and endometriosis: Systematic review and meta-analysis. Environment International. 2019;123:209-223\n'},{id:"B8",body:'\nLouis GM, Weiner JM, Whitcomb BW, Sperrazza R, Schisterman EF, Lobdell DT, et al. Environmental PCB exposure and risk of endometriosis. Human Reproduction. 2005;20:279-285\n'},{id:"B9",body:'\nPorpora MG, Ingelido AM, Domenico AD, Ferro A, Crobu M, Pallante D, et al. Increased levels of polychlorobiphenyls in Italian women with endometriosis. Chemosphere. 2005;63(8):1361-1367\n'},{id:"B10",body:'\nReddy BS, Rozati R, Reddy S, Kodampur S, Reddy P, Reddy R. High plasma concentrations of polychlorinated biphenyls and phthalate esters in women with endometriosis: A prospective case control study. Fertility and Sterility. 2006;85:775-779\n'},{id:"B11",body:'\nLebel G, Dodin S, Ayotte P, Marcoux S, Ferron LA, Dewailly E. Organochlorine exposure and the risk of endometriosis. Fertility and Sterility. 1998;69:221-228\n'},{id:"B12",body:'\nPauwels A, Schepens PJC, Hooghe TD, Delbeke L, Dhont M, Brouwer A, et al. The risk if endometriosis and exposure to dioxins and polychlorinated biphenyls: A case-control study of infertile women. Human Reproduction. 2001;16:2050-2055\n'},{id:"B13",body:'\nTsukino H, Hanaoka T, Sasaki H, Motoyama H, Hiroshima M, Tanaka T, et al. Associations between serum levels of selected organochlorine compounds and endometriosis in infertile Japanese women. Environmental Research. 2005;99:118-125\n'},{id:"B14",body:'\nAnger DL, Foster WG. The link between environmental toxicant exposure and endometriosis. Frontiers in Bioscience. 2008;13:1578-1593\n'},{id:"B15",body:'\nFoster WG, Agarwal SK. Environmental contaminants and dietary factors in endometriosis. Annals of the New York Academy of Sciences. 2002;955:213-229\n'},{id:"B16",body:'\nFoster WG. Do environmental contaminants adversely affect human reproductive physiology? Journal of Obstetrics and Gynaecology Canada. 2003;25:33-44\n'},{id:"B17",body:'\nFoster WG. Endocrine toxicants including 2,3,7,8-terachlorodibenzo-p-dioxin (TCDD) and dioxin-like chemicals and endometriosis: Is there a link? Journal of Toxicology and Environmental Health. Part B, Critical Reviews. 2008;11:177-187\n'},{id:"B18",body:'\nVabre P, Gatimel N, Moreau J, Gayrard V, Picard-Hagen N, Parinaud J, et al. Environmental pollutants, a possible etiology for premature ovarian insufficiency: A narrative review of animal and human data. Environmental Health. 2017;16:37\n'},{id:"B19",body:'\nFaroon O, Ruiz P. Polychlorinated biphenyls: New evidence from the last decade. Toxicology and Industrial Health. 2016;32:1825-1847\n'},{id:"B20",body:'\nBruner-Tran KL, Osteen KG. Dioxin-like PCBs and endometriosis. Systems Biology in Reproductive Medicine. 2010;56:132-146\n'},{id:"B21",body:'\nKorach KS, Sarver P, Chae K, McLachlan JA, McKinney JD. Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: Conformationally restricted structural probes. Molecular Pharmacology. 1988;33:120-126\n'},{id:"B22",body:'\nMoore M, Mustain M, Daniel K, Chen I, Safe S, Zacharewski T, et al. Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum. Toxicology and Applied Pharmacology. 1997;142:160-168\n'},{id:"B23",body:'\nPorpora MG, Medda E, Abballe A, Bolli S, De Angelis I, di Domenico A, et al. Endometriosis and organochlorinated environmental pollutants: A case-control study on Italian women of reproductive age. Environmental Health Perspectives. 2009;117:1070-1075\n'},{id:"B24",body:'\nCai LY, Izumi S, Suzuki T, Goya K, Nakamura E, Sugiyama T, et al. Dioxins in ascites and serum of women with endometriosis: A pilot study. Human Reproduction. 2010;26(1):117-126\n'},{id:"B25",body:'\nTrabert B, De Roos AJ, Schwartz SM, Peters U, Scholes D, Barr DB, et al. Non-dioxin-like polychlorinated biphenyls and risk of endometriosis. Environmental Health Perspectives. 2010;118:1280-1285\n'},{id:"B26",body:'\nPloteau S, Antignac JP, Volteau C, Marchand P, Vénisseau A, Vacher V, et al. Distribution of persistent organic pollutants in serum, omental, and parietal adipose tissue of French women with deep infiltrating endometriosis and circulating versus stored ratio as new marker of exposure. Environment International. 2016;97:125-136\n'},{id:"B27",body:'\nLouis GM, Peterson CM, Chen Z, Hediger ML, Croughan MS, Sundaram R, et al. Perfluorochemicals and endometriosis: The ENDO study. Epidemiology. 2012;23:799-805\n'},{id:"B28",body:'\nMartínez-Zamora MA, Mattioli L, Parera J, Abad E, Coloma JL, van Babel B, et al. Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis. Human Reproduction. 2015;30:1059-1068\n'},{id:"B29",body:'\nSimsa P, Mihalyi A, Schoeters G, Koppen G, Kyama CM, Den Hond EM, et al. Increased exposure to dioxin-like compounds is associated with endometriosis in a case-control study in women. Reproductive Biomedicine Online. 2010;20:681-688\n'},{id:"B30",body:'\nVichi S, Medda E, Ingelido AM, Ferro A, Resta S, Porpora MG, et al. Glutathione transferase polymorphisms and risk of endometriosis associated with polychlorinated biphenyls exposure in Italian women: A gene-environment interaction. Fertility and Sterility. 2012;97:1143-1151\n'},{id:"B31",body:'\nBuck Louis GM, Chen Z, Peterson CM, Hediger ML, Croughan MS, Sundaram R, et al. Persistent lipophilic environmental chemicals and endometriosis: The ENDO study. Environmental Health Perspectives. 2012;120:811-816\n'},{id:"B32",body:'\nMatsuzaka Y, Kikuti YY, Goya K, Suzuki T, Cai LY, Oka A, et al. Lack of an association human dioxin detoxification gene polymorphisms with endometriosis in Japanese women: Results of a pilot study. Environmental Health and Preventive Medicine. 2012;17:512-517\n'},{id:"B33",body:'\nSinaii N, Cleary SD, Younes N, Ballweg ML, Stratton P. Treatment utilization for endometriosis symptoms: A cross-sectional survey study of lifetime experience. Fertility and Sterility. 2007;87:1277-1286\n'},{id:"B34",body:'\nGreene R, Stratton P, Cleary SD, Ballweg ML, Sinaii N. Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertility and Sterility. 2009;91:32-39\n'},{id:"B35",body:'\nBruner-Tran KL, Ding T, Osteen KG. Dioxin and endometrial progesterone resistance. Seminars in Reproductive Medicine. 2010;28:59-68\n'},{id:"B36",body:'\nBruner-Tran KL, Rier SE, Eisenberg E, Osteen KG. The potential role of environmental toxins in the pathophysiology of endometriosis. Gynecologic and Obstetric Investigation. 1999;48(Suppl 1):45-56\n'},{id:"B37",body:'\nRier SE, Tuner WE, Martin DC, Morris R, Lucier GW, Clark GC. Serum levels of TCDD and dioxin-like chemicals in rhesus monkeys chronically exposed to dioxin: Correlation of increased serum PCB levels with endometriosis. Toxicological Sciences. 2001;59:147-159\n'},{id:"B38",body:'\nYang JZ, Agarwal SK, Foster WG. Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the Cynomolgus monkey. Toxicological Sciences. 2000;56:374-381\n'},{id:"B39",body:'\nHuang Q , Chen Y, Chen Q , Zhang H, Lin Y, Zhu M, et al. Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine-inflammation interactions. Archives of Toxicology. 2017;91:1915-1924\n'},{id:"B40",body:'\nWang Y, Chen H, Wang N, Guo H, Fu Y, Xue S, et al. Combined 17β-estradiol with TCDD promotes M2 polarization of macrophages in the endometriotic milieu with aid of the interaction between endometrial stromal cells and macrophages. PLoS One. 2015;10:e0125559\n'},{id:"B41",body:'\nResuehr D, Glore DR, Taylor HS, Bruner-Tran KL, Osteen KG. Progesterone-dependent regulation of endometrial cannabinoid receptor type 1 (CB1-R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Fertility and Sterility. 2012;98:948.e941-956.e941\n'},{id:"B42",body:'\nWilling C, Peich M, Danescu A, Kehlen A, Fowler PA, Hombach-Klonisch S. Estrogen-independent actions of environmentally relevant AHR-agonists in human endometrial epithelial cells. Molecular Human Reproduction. 2011;17:115-126\n'},{id:"B43",body:'\nHu T, Yao M, Fu X, Chen C, Wu R. Polychlorinated biphenyl 104 promotes migration of endometrial stromal cells in endometriosis. Toxicology Letters. 2018;290:19-28\n'},{id:"B44",body:'\nCooney MA, Buck Louis GM, Hediger ML, Vexler A, Kostyniak PJ. Organochlorine pesticides and endometriosis. Reproductive Toxicology. 2010;30:365-369\n'},{id:"B45",body:'\nUpson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, et al. Organochlorine pesticides and risk of endometriosis: Findings from a population-based case-control study. Environmental Health Perspectives. 2013;121:1319-1324\n'},{id:"B46",body:'\nChiappini F, Bastón JI, Vaccarezza A, Singla JJ, Pontillo C, Miret N, et al. Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by hexachlorobenzene in human endometrial stromal cells. Biochemical Pharmacology. 2016;109:91-104\n'},{id:"B47",body:'\nCalafat AM, Kuklenyik Z, Caudill SP, Reidy JA, Needham LL. Perfluorochemicals in pooled serum samples from United States residents in 2001 and 2002. Environmental Science & Technology. 2006;40:2128-2134\n'},{id:"B48",body:'\nGuruge KS, Taniyasu S, Yamashita N, Wijeratna S, Mohotti KM, Seneviratne HR, et al. Perfluorinated organic compounds in human blood serum and seminal plasma: A study of urban and rural tea worker populations in Sri Lanka. Journal of Environmental Monitoring. 2005;7:371-377\n'},{id:"B49",body:'\nBach CC, Vested A, Jørgensen KT, Bonde JP, Henriksen TB, Toft G. Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: A systematic review. Critical Reviews in Toxicology. 2016;46:735-755\n'},{id:"B50",body:'\nKielsen K, Shamim Z, Ryder LP, Nielsen F, Grandjean P, Budtz-Jørgensen E, et al. Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates. Journal of Immunotoxicology. 2016;13:270-273\n'},{id:"B51",body:'\nLiu G, Dhana K, Furtado JD, Rood J, Zong G, Liang L, et al. Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: A prospective study. PLoS Medicine. 2018;15:e1002502\n'},{id:"B52",body:'\nCampbell S, Raza M, Pollack AZ. Perfluoroalkyl substances and endometriosis in us women in NHANES 2003-2006. Reproductive Toxicology. 2016;65:230-235\n'},{id:"B53",body:'\nRashtian J, Chavkin DE, Merhi Z. Water and soil pollution as determinant of water and food quality/contamination and its impact on female fertility. Reproductive Biology and Endocrinology. 2019;17:5\n'},{id:"B54",body:'\nRochester JR. Bisphenol a and human health: A review of the literature. Reproductive Toxicology. 2013;42:132-155\n'},{id:"B55",body:'\nItoh H, Iwasaki M, Hanaoka T, Sasaki H, Tanaka T, Tsugane S. Urinary phthalate monoesters and endometriosis in infertile Japanese women. Science of the Total Environment. 2009;408:37-42\n'},{id:"B56",body:'\nUpson K, Sathyanarayana S, De Roos AJ, Koch HM, Scholes D, Holt VL. A population-based case-control study of urinary bisphenol A concentrations and risk of endometriosis. Human Reproduction. 2014;29:2457-2464\n'},{id:"B57",body:'\nCobellis L, Colacurci N, Trabucco E, Carpentiero C, Grumetto L. Measurement of bisphenol A and bisphenol B levels in human blood sera from healthy and endometriotic women. Biomedical Chromatography. 2009;23:1186-1190\n'},{id:"B58",body:'\nItoh H, Iwasaki M, Hanaoka T, Sasaki H, Tanaka T, Tsugane S. Urinary bisphenol-A concentration in infertile Japanese women and its association with endometriosis: A cross-sectional study. Environmental Health and Preventive Medicine. 2007;12:258-264\n'},{id:"B59",body:'\nPednekar PP, Gajbhiye RK, Patil AD, Surve SV, Datar AG, Balsarkar GD, et al. Estimation of plasma levels of bisphenol-A & phthalates in fertile & infertile women by gas chromatography-mass spectrometry. The Indian Journal of Medical Research. 2018;148:734-742\n'},{id:"B60",body:'\nJones RL, Lang SA, Kendziorski JA, Greene AD, Burns KA. Use of a mouse model of experimentally induced endometriosis to evaluate and compare the effects of bisphenol A and bisphenol AF exposure. Environmental Health Perspectives. 2018;126:127004\n'},{id:"B61",body:'\nForte M, Mita L, Cobellis L, Merafina V, Specchio R, Rossi S, et al. Triclosan and bisphenol A affect decidualization of human endometrial stromal cells. Molecular and Cellular Endocrinology. 2016;422:74-83\n'},{id:"B62",body:'\nSilva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, et al. Urinary levels of seven phthalate metabolites in the U.S. population from the national health and nutrition examination survey (NHANES) 1999-2000. Environmental Health Perspectives. 2004;112:331-338\n'},{id:"B63",body:'\nTyrrell J, Melzer D, Henley W, Galloway TS, Osborne NJ. Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010. Environment International. 2013;59:328-335\n'},{id:"B64",body:'\nMeeker JD, Ferguson KK. Urinary phthalate metabolites are associated with decreased serum testosterone in men, women, and children from NHANES 2011-2012. The Journal of Clinical Endocrinology and Metabolism. 2014;99(11):4346-4352\n'},{id:"B65",body:'\nLague E, Tremblay JJ. Antagonistic effects of testosterone and the endocrine disruptor mono-(2-ethylhexyl) phthalate on INSL3 transcription in Leydig cells. Endocrinology. 2008;149:4688-4694\n'},{id:"B66",body:'\nNazir S, Usman Z, Imran M, Lone KP, Ahmad G. Women diagnosed with endometriosis show high serum levels of diethyl hexyl phthalate. Journal of Human Reproductive Sciences. 2018;11:131-136\n'},{id:"B67",body:'\nBuck Louis GM, Peterson CM, Chen Z, Croughan M, Sundaram R, Stanford J, et al. Bisphenol A and phthalates and endometriosis: The endometriosis: Natural history, diagnosis and outcomes study. Fertility and Sterility. 2013;100:162-169\n'},{id:"B68",body:'\nHuang PC, Tsai EM, Li WF, Liao PC, Chung MC, Wang YH, et al. Association between phthalate exposure and glutathione S-transferase M1 polymorphism in adenomyosis, leiomyoma and endometriosis. Human Reproduction. 2010;25:986-994\n'},{id:"B69",body:'\nWeuve J, Hauser R, Calafat AM, Missmer SA, Wise LA. Association of exposure to phthalates with endometriosis and uterine leiomyomata: Findings from NHANES, 1999-2004. Environmental Health Perspectives. 2010;118:825-832\n'},{id:"B70",body:'\nHuang PC, Li WF, Liao PC, Sun CW, Tsai EM, Wang SL. Risk for estrogen-dependent diseases in relation to phthalate exposure and polymorphisms of CYP17A1 and estrogen receptor genes. Environmental Science and Pollution Research International. 2014;21:13964-13973\n'},{id:"B71",body:'\nUpson K, Sathyanarayana S, De Roos AJ, Thompson ML, Scholes D, Dills R, et al. Phthalates and risk of endometriosis. Environmental Research. 2013;126:91-97\n'},{id:"B72",body:'\nKubiszeski EH, de Medeiros SF, da Silva Seidel JA, Barbosa JS, Galera MF, Galera BB. Glutathione s-transferase M1 and T1 gene polymorphisms in Brazilian women with endometriosis. Journal of Assisted Reproduction and Genetics. 2015;32:1531-1535\n'},{id:"B73",body:'\nKim SH, Cho S, Ihm HJ, Oh YS, Heo SH, Chun S, et al. Possible role of phthalate in the pathogenesis of endometriosis: In vitro, animal, and human data. The Journal of Clinical Endocrinology and Metabolism. 2015;100:E1502-E1511\n'},{id:"B74",body:'\nDart AE, Wells CM. P21-activated kinase 4—Not just one of the PAK. European Journal of Cell Biology. 2013;92:129-138\n'},{id:"B75",body:'\nCho YJ, Park SB, Han M. Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal cells in vitro. Molecular and Cellular Endocrinology. 2015;407:9-17\n'},{id:"B76",body:'\nPollack AZ, Louis GM, Chen Z, Peterson CM, Sundaram R, Croughan MS, et al. Trace elements and endometriosis: The ENDO study. Reproductive Toxicology. 2013;42:41-48\n'},{id:"B77",body:'\nLai GL, Yeh CC, Yeh CY, Chen RY, Fu CL, Chen CH, et al. Decreased zinc and increased lead blood levels are associated with endometriosis in Asian women. Reproductive Toxicology. 2017;74:77-84\n'},{id:"B78",body:'\nSilva N, Tennekoon K, Senanayake H, Samarakoon S. Metalloestrogen cadmium stimulates proliferation of stromal cells derived from the eutopic endometrium of women with endometriosis. Taiwanese Journal of Obstetrics & Gynecology. 2013;52:540-545\n'},{id:"B79",body:'\nGordts S, Koninckx P, Brosens I. Pathogenesis of deep endometriosis. Fertility and Sterility. 2017;108:872.e871-885.e871\n'},{id:"B80",body:'\nWykes CB, Clark TJ, Khan KS. Accuracy of laparoscopy in the diagnosis of endometriosis: A systematic quantitative review. BJOG. 2004;111:1204-1212\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Shay M. Freger",address:null,affiliation:'
Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
'},{corresp:"yes",contributorFullName:"Warren G. Foster",address:"fosterw@mcmaster.ca",affiliation:'
Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
'}],corrections:null},book:{id:"9785",type:"book",title:"Endometriosis",subtitle:null,fullTitle:"Endometriosis",slug:"endometriosis",publishedDate:"January 14th 2021",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-465-0",printIsbn:"978-1-83962-464-3",pdfIsbn:"978-1-83962-466-7",reviewType:"peer-reviewed",numberOfWosCitations:2,isAvailableForWebshopOrdering:!0,editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"189"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"70843",type:"chapter",title:"The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined",slug:"the-link-between-environmental-toxicant-exposure-and-endometriosis-re-examined",totalDownloads:765,totalCrossrefCites:1,signatures:"Shay M. 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1. Introduction
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Endometriosis an estrogen dependent disease characterized by ectopic growth of endometrial glands and stroma outside of the uterine cavity. It is estimated that endometriosis may affect anywhere from 5 to 45% of all women [1]. Although retrograde menstruation has become the most widely accepted theory for the development of endometriosis [2], it cannot account for endometriosis in distant organs such as the lung and brain. Therefore, alternative explanations are sought.
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While the cause of endometriosis remains unknown, it most likely arises from a multifaceted origin involving the interaction of environment and genetics [3]. Among the different hypotheses advanced, a growing body of literature suggests that environmental factors including environmental toxicants may play a role in the pathophysiology of endometriosis. Lifestyle and medication use point to a role for environmental factors in endometriosis. While alcohol consumption and cigarette smoking have been associated with lower endometriosis risk [4], developmental exposure to diethylstilbestrol and early life exposure to soy formula as well as alcohol consumption in adulthood was linked with an increased risk of endometriosis [4, 5]. Support for an environmental toxicant influence on the development of endometriosis surged with the report of endometriosis in rhesus monkeys treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [6]. Evidence of estrogen mimicry, dysregulation of steroid signaling, and immune modulation by environmental toxicants such as the persistent organic pollutants including the polychlorinated biphenyls (PCBs), dioxins and dioxin like compounds, pesticides, plasticizers (phthalates and bisphenol A), and some metals has led some to hypothesize that human exposure to environmental toxicants may play an important role in reproductive health including endometriosis [3]. Although a recent systematic review and meta-analysis suggests a possible link between exposure to chlorinated organic chemicals and endometriosis [7], we postulate that the role of exposure to environmental toxicants in the pathophysiology of endometriosis remain uncertain.
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Potential associations between exposure to environmental toxicants and women with endometriosis have been equivocal with several finding positive associations [8, 9, 10] whereas others were unable to document an association [11, 12, 13]. Since our last review of the subject [14, 15, 16, 17] numerous studies have emerged suggesting a potential link between environmental toxicant exposure and endometriosis [7, 18]. Herein, we describe a systematic review and critical appraisal of the recent literature linking exposure to environmental toxicants and endometriosis using a modified weight-of-evidence approach to evaluate the strength of potential associations.
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2. Approach
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We conducted a systematic review of the literature between 2008 and present, to capture publications since our last review of the subject [14, 17]. An electronic search was performed using PubMed and web of science between October and November 2019. The following search terms were employed: endometriosis and environmental contaminants, environmental chemicals, environmental toxicants, endocrine disrupters, dioxins, polychlorinated biphenyls (PCBs), phthalates, bisphenol A, and metals. Inclusion criteria included biomonitoring, epidemiology studies reporting chemical concentrations in women with endometriosis compared to a reference population and associated risk. We also included articles describing experimental animal studies and in vitro experiments designed to explore the effect of chemical exposure on endometriotic lesion survival, growth, and to elucidate potential mechanisms relevant to human health. Review papers, meeting summaries, commentaries were excluded as were articles written in languages other than English. Article titles were downloaded into an Excel spreadsheet and duplicate titles excluded. Articles meeting inclusion and exclusion criteria were decided by review of article titles and abstracts by both authors. Disagreements were resolved through discussion. Articles meeting inclusion criteria were printed in full and read by both authors.
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3. Results
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Our electronic search of the literature revealed 67 articles from which four articles with duplicate titles were excluded (Figure 1). We further excluded six review articles. An additional seven articles were excluded because they either did not report chemical concentrations or associated risk for the development of endometriosis. Consequently, 50 articles were retained for full assessment. The largest group of articles addressed the association between exposure to chlorinated organic compounds including polychlorinated biphenyls (PCBs), dioxins, and dioxin-like compounds with relatively few studies exploring the link between pesticide exposure and endometriosis. Of the chemicals with comparatively short half-lives relative to the chlorinated organic compounds and potential to disrupt endocrine signaling pathways, several reports linking phthalate esters and bisphenol A with endometriosis were found in our search whereas relatively few studies involving perfluoroalkyl compounds and metals studies were found.
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Figure 1.
Flow diagram summarizing the process of candidate article title identification in our electronic literature searches (PubMed and Web of Science) conducted between January 2018 and February 2019, screening, and article selection vs. exclusion. The number of articles included vs. excluded and reasons for exclusion are indicated.
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3.1 Polychlorinated biphenyls (PCBs), dioxin and dioxin-like compounds
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PCBs are one of the most widely produced chemicals worldwide, with millions of pounds being produced globally over the last decade alone [19] for use a coolants in electrical transformers. With 209 possible congeners, PCB toxicity is dependent on chemical structure. For example, non-ortho or mono-ortho PCBs are far more toxic due to the loss of chlorine atoms on the 2,2′,6,6′ of the benzene rings [20]. Due to their diverse structures, PCBs share similar characteristics to estrogen, allowing them to have both agonistic and anti-estrogenic activity [21, 22]. PCBs have been known to disrupt several organs and tissue types throughout the human body; with particular damage to the liver, kidney, and the endocrine system [19]. Our search revealed several studies primarily focused on PCB exposure and endometriosis and additional studies that explored the link between dioxin and dioxin-like compounds and endometriosis (Table 1). Since these compounds are frequently found together in human tissues, we will discuss them together.
Increased risk of endometriosis for DL-PCB-118 (OR = 3.79; 95% CI, 1.61–8.91), NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10) were all significant in case versus controls.
PCB concentrations were higher in peritoneal fluid than serum. However, the total TEQ LOD and dioxin-like PCBs were not significantly different between women with endometriosis and the controls.
Several PCB congeners were associated with significantly lower risk (PCB 170 3rd quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.9) PCN196 (3rd quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7), PCB201 (2nd quartile vs. lowest: OR = 0.5; 95% CI, 0.3–0.8; and 3rd quartile vs. lowest: OR = 0.4; 95% CI, 0.2–0.7) but not summed values (PCBs 170, 196, 201; OR = 1.3, CI 0.8–2.2) and estrogenic PCBs (OR = 1.1; 95% CI, 0.8–1.4).
Significant correlations for PCB concentrations within the three biological compartments omental versus peritoneal adipose tissue were found (p < 0.0001). 137.1 vs. 147.9 ng/g l.w. for sum of 6 NDL-PCB. Adipose vs. serum: WHO-TEQ2005 DL-PCB = 3.6 pg/g l.w., sum of 6 NDL-PCB = 81.1 ng/g l.w.
Dioxins and DL-PCBs were significantly higher in patients with deep infiltrating endometriosis; TCDD, PeCDD, PeCDF were the most significant p < 0.01 for each compound. PCB-126 (PCB-114 p < 0.05; PCB-156 p < 0.05; PCB-189 p = 0.04; PCB-126 p < 0.01).
DLC concentrations were marginally higher in patients with endometriosis (22.3±9.3 pg vs. 20.5±10.8 pg) and higher plasma levels of DLC were linked to a higher risk of endometriosis (aOR = 2.44; 95% CI 1.04–5.70; p = 0.04) adjusted for age. Moderate–severe endometriosis cases only (OR = 3.01; 95% CI 1.06–9.04; p = 0.03)
With the presence of the GSTP1 wild type genotype, medium-high levels of PCB 153, high levels of PCB 180 and total PCBS were significantly associated with endometriosis risk (OR = 6.00; 95% CI, 1.88–19.18 and OR = 9.08; 95% CI, 2.14–44.4, respectively).
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Table 1.
Summary of exposures and outcomes from biomonitoring studies designed to quantify the concentration of polychlorinated biphenyl congeners, dioxins, dioxin-like compounds (DLCs) and non-dioxin-like compounds (NDL) in women with endometriosis compared to healthy controls.
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In a pilot case–control study [24], involving 17 women (10 cases; 7 controls), superficial endometriosis was present in 90% of the cases. Of the 29 congeners measured in this study, both polychlorinated dibenzofurans (PCDFs) and dioxin-like (DL) -PCBs showed no significant difference between the case and control [24]. However, both were elevated in peritoneal fluid relative to the serum, with the reverse seen in polychlorinated dibenzo-p-dioxins (PCDDs) [24]. Both PCDDs and PCDFs in peritoneal fluid were significantly associated with an increased risk of endometriosis [24]. Although a potential association was found, the small sample size, the authors did not adjust for other factors such as age that have previously been shown to affect endometriosis risk. Hence, confidence in the findings from this pilot study is low. In contrast, results of a case–control study [23] of 158 Italian women (80 cases; 78 controls), revealed that both non-dioxin-like (NDL)-PCBs and DL-PCBs levels were significantly elevated in women with laparoscopically and histologically confirmed endometriosis. An increased risk of endometriosis was found for DL-PCBs (PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], and NDL-PCBs including PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10)). No significant associations were observed with respect to hexachlorobenzene (HCB) or to the sum of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs expressed as total toxic equivalent quotients (TEQs). PCB-101, PCB-156, and PCB-170 were all shown to be statistically elevated, with PCB-52, PCB-118, PCB-138, PCB-153, and PCB-180 showing a highly significant difference. All four stages and endometriosis implant localizations (peritoneal, deep, or ovarian) were analyzed, with no significant differences detected. However, the lack of adjustment for potential confounding and failure to account for multiple comparisons are important limitations of this study. IN another study [29], DLC concentrations were quantified in plasma samples using the dioxin-responsive chemical-activated luciferase expression bioassay (CALUX). Blood samples were collected prior to laparoscopic surgery from women with endometriosis (n = 96) and control patients with a normal pelvis (n = 106). A marginal increase in DLC compound concentrations in endometriosis patients relative to controls (22.3 ± 9.3 pg, versus 20.5 ± 10.8 pg CALUX-TEQ/g lipid) was reported [29]. After adjusting plasma concentrations for age only, an increased risk for endometriosis was demonstrated for high concentrations of DLC (OR = 2.44; 95% CI 1.04–5.70, p = 0.04) and when considering moderate to severe endometriosis (OR = 3.01; 95% CI 1.06–9.04, p = 0.03). While the authors adjusted for age, adjustment for BMI, parity, and breast feeding was not undertaken. Thus, these results although suggestive must be interpreted with caution.
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While several studies have provided evidence of a potential link significant associations between women with endometriosis and PCB levels could not be demonstrated by other investigators [25, 28, 31]. No significant association between PCBs and endometriosis risk was found in a study of 789 patients (251 cases; 538 controls); with 20 PCB congers measured in serum from surgically confirmed cases [25]. While the odds ratios (ORs) for several PCB congeners did show significant levels above and below the null; however, there was no specific pattern associated with endometriosis risk. Several PCBs were quantified in the serum of 473 women in an operative cohort (190 cases; 283 controls) and 127 patients from a general population cohort (14 cases; 113 controls), using omental fat in the operative cohort and serum in both [31]. Results were adjusted for confounding variables such as age, BMI, breast-feeding, cotinine, and lipids. Among the 35 PCB congers analyzed, geometric mean serum PCB levels were found to be inversely related in terms of risk in the operative cohort, with the opposite seen in the population cohort [31]. A similar relationship can be seen in omental fat, with sum PCB levels showing significantly higher levels in the non-endometriosis patients relative to the controls. Limitations of this study include the small number of women with endometriosis in the case population (only 11% of women had endometriosis), possible bias through the use of telephone directories, and use of controls without surgical confirmation of absence of disease suggest that results be interpreted with caution. The relationship between exposure to DLCs and deep infiltrating endometriosis (DIE) was explored in a case–control study of 30 cases and 30 controls [28]. Disease status was determined by clinical examination, magnetic resonance imaging (MRI), and transvaginal ultrasonography (TVUS), whereas the control population underwent laparoscopic surgery for adnexal benign gynecological disease. DLCs were analyzed omentum adipose tissue in both groups. The results suggest a significant increase of both dioxins and PCBs relative to the control, with the most toxic forms showing a significant difference (2,3,7,8-TCDD and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]; p < 0.01) [28]. Furthermore, 2,3,4,7,8-PeCDF was also significantly higher and four of the most toxic PCB congeners (PCB 144, 156, 189, 126) had toxic equivalence values (TEQ) that were statistically higher in DIE patients [28]. However, no differences were seen when the data were adjusted for age, breast feeding, and BMI. Limitations of this study include small sample size, and homogeneity of the sample population [28].
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A biomonitoring study conducted in France [26], measured the concentrations of PCBs in serum, peritoneal and omental adipose tissue of 113 adult French women with deep infiltrating endometriosis (DIE) (45 controls, 68 cases). There was a significant difference between omental versus peritoneal adipose tissue PCB concentrations (p < 0.0001). Similar trends were seen is peritoneal adipose tissue versus serum levels, with PCBs showing the highest level of significance in terms of concentration differences.
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Potential gene–environment interaction among women with endometriosis was explored [30]. Specifically, the relationship between glutathione transferase (GST) gene polymorphisms PCB concentrations in a study of 343 Italian women (181 cases; 162 controls). Ability glutathione enzymes to regulate oxidative free radicals and thus oxidative stress and therefore genetic polymorphisms may influence tissue capacity to manage the damaging effects oxidative stress, in turn influencing disease susceptibility. No significant difference in genotype distribution (GSTM1, GSTA1, and GSTP1) between case and control patients could be elicited [30]. However, the GSTP1 wild-type with medium-high blood levels of PCB153, high levels of PCB180, or total PCB levels, showed a significant increase in potential risk, while GSTT1 null was negatively associated with the disease [30]. The potential association between five microsatellites and 28 single nucleotide polymorphisms among 10 dioxin detoxification genes (aryl hydrocarbon receptor (AhR), AHRR, ARNT, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) was examined in 242 women (100 case; 143 control) from Japan [32]. Accounting for disease stages I-IV, BMI, and smoking, no significant association was seen between the polymorphisms and the contribution to the etiology of endometriosis. Taken together, these data suggest that genetic polymorphisms in detoxification enzymes do not modulate endometriosis risk.
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Establishing a link between exposure to environmental toxicants and endometriosis using epidemiology and biomonitoring is difficult owing to challenges in diagnosis of endometriosis [33], lengthy diagnostic delays [34], and high prevalence of endometriosis in asymptomatic women [1] and thus the potential for misclassification error is high. Therefore, animal studies have been employed to better understand the potential hazard posed between toxicant exposure and endometriosis. Developmental exposure of mice to TCDD induced a progesterone-resistant phenotype in adult animals that persisted across generations [35]. Results of this study suggest that TCDD induced activation of the aryl hydrocarbon signaling pathway induces dysregulation of expression of tissue remodeling enzymes, and contributes to the inflammatory responses, cell migration, and proliferation seen in endometriosis patients. These data are supported by prior animal studies demonstrating PCB and dioxin effects in animal models of endometriosis [36, 37, 38].
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Tissue culture studies have been employed to elucidate potentially important toxicant regulated mechanisms. PCBs have been linked to an increased estradiol synthesis and creating an inflammatory milieu through the production of interleukin (IL)-6 and IL-8 [39]. Primary cultures of endometrial stromal cells (ESCs) were treated with both DL-PCBs and NDL-PCBs. Dioxin-like CB126 treatment increased 17β-estradiol (E2) biosynthesis in a dose dependent manner. CB126 exposure also increased 17β-hydroxysteroid dehydrogenase 7 (HSD17B7) as well as decreased methylation of the HSD17B7 promoter leading to an increase in expression. Inflammatory markers were also elevated in cultured endometrial stromal cells. Increased inflammation and E2 synthesis were demonstrated in a mouse model of endometriosis [39]. Although PCB has shown to increase E2 biosynthesis, combining 17β-Estradiol with TCDD showed a synergistic effect and induces M2 activation with macrophages co-cultured with ESCs. STAT3 and P38 phosphorylation in macrophages were also increased differentiation of M2 macrophages, leading to an inflammatory milieu [40]. Several studies also analyzed the impact of TCDD exposure on progesterone-dependent mechanisms. TCDD was found to induce cannabinoid receptor type 1 CB1-R mRNA expression in endometrial stromal cells and steroid-induced expression of the gene was inhibited. Through the use of tissue obtained from women with and without endometriosis, TCDD treatment-induced dysregulation of cannabinoid signaling, immune cell migration into the endometrium during embryo uterine attachment [41] and thus we propose could be an important mechanism in the pathophysiology of endometriosis. PCB was also seen to activate endogenous aryl hydrocarbon receptor (AhR) signaling pathway in immortalized human telomerase reverse transcriptase (hTERT) endometrial epithelial cell (hTERT-EEC), specific to time, concentration, and congener. The changes induced were modulated by changes in estrogen levels, in turn increasing cell migration by hTERT-EEC. Proteomic analysis also identified cell stress responses and metabolism markers (such as heat shock proteins (HSP) 27 and HSP 70) [42]. These proteins are both critical markers for the regulation of apoptosis and cellular stress response pathways. In another study [43] primary cultures of ESCs from both case and control patients showed that PCB-104 exposure affects cell migration, invasion and resultant gene expression. Treatments induced a significant increase in cell migration and invasion of ESCs. Enzyme-linked immunosorbent assays showed a time and dose dependent increase in matrix metalloproteinase 3 (MMP-3) and MMP-10 protein in ESCs, whereas MMP-2, MMP-9, TIMP-2, E-cadherin, Snail and Slug did not. MMP-3 contributes to the breakdown of the extracellular matrix and promotes tissue remodeling and migration [43]. The results from this study suggest that PCB-104 increased migration and invasion of ESCs through increasing MMP-3 and MMP-10 [43]. Taken together, results from tissue culture studies elucidate PCB and dioxin induced dysregulation of mechanisms potentially important in the pathophysiology of endometriosis.
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In summary, several studies demonstrated a potential association between exposure to PCBs, dioxins, and dioxin-like compounds and increased risk of endometriosis; however, important study limitations decrease confidence in these study findings. Moreover, several studies were unable to evoke evidence of an association between exposure to these toxicants. While, animal studies are few, results from these studies provide evidence of biological plausibility. Results of tissue culture studies also provide evidence that PCBs and dioxins adversely affect mechanistic pathways important in the pathophysiology of endometriosis although the effective concentrations exceed human exposure. Consequently, we suggest that there is weak evidence linking exposure to PCBs and dioxin and DL-PCBs in the pathophysiology of endometriosis.
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3.2 Pesticides
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Chlorinated organic pesticides (COPs) resist degradation in the environment, are lipophilic and thus bioaccumulate in adipose tissues, and concentrations are biomagnified with increasing trophic level. Moreover, COPs are able to travel long distances and remain stable for several decades in the environment, and thus widespread human exposure to these chemicals has frequently been documented. Despite widespread human exposure, the relationship between pesticides and endometriosis risk in general are equivocal.
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The concentrations of six COP levels were measured with gas chromatography and electron-capture, in blood samples of laparoscopically confirmed cases of endometriosis [44]. Results showed that aromatic fungicides had a five-fold increase in risk (aOR = 5.3; 95% CI, 1.2–23.6) when comparing the highest and lowest tertile after adjusting for smoking and serum lipids [44]. Chlordane (t-nonachlor) (aOR = 4.6; 95% CI, 0.5–41.6) and HCB (aOR = 6.4; 95% CI, 1.0–42.8) showed a similar trend [44]. Aldrin, β-hexachlorocyclohexane (β-BHC) and mirex also had increased ORs; however, few women had concentrations above the limit of detection preventing further analysis. Two other studies yielded similar results. Specifically, hexachlorocyclohexane (HCH) was associated with an increased risk of endometriosis in a large study with 248 surgically confirmed endometriosis cases and 538 controls [45]. β-HCH concentrations were significantly elevated in the serum (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0–2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8–2.4), as well as for mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0–2.2). The results were adjusted for participant age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Although trends were seen throughout multiple forms of endometriosis, the strongest association was seen in women with ovarian endometriosis. Similarly, γ-hexachlorocyclohexane (γ-HCH) had a significant association with endometriosis risk (adjusted OR (AOR) for age, body mass index, breast-feeding conditional on parity, cotinine, and lipids = 1.27; 95% CI: 1.01–1.59) [31]. Although these studies provide evidence for a link between exposure to different pesticides and increased risk of endometriosis, there are several limitations to note. In particular, while the authors adjusted their data for some potential confounding variables none appeared to adjust for BMI. Moreover, since multiple pesticides were quantified in each study, correction for multiple comparisons would add confidence to the findings and exclude the potential for type I error. Furthermore, the lack of a dose–response relationship [45] suggests that chance discovery cannot be excluded.
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We found no recent animal studies and only one in vitro study was found. HCB treatment enhanced MMP-2 and MMP-9 activities in human endometrial stromal cell line T-HESC, primary cultures of Human Uterine Fibroblast (HUF), and ESCs [46]. Specifically, MMP-2 was only elevated in ESCs, whereas MMP-9 was elevated in all models. An increase in COX-2 and prostaglandin receptor-4 expression, prostaglandin E2 secretion and the c-Src kinase activation in T-HESC was also seen after HCB exposure. The results suggest that HCB may promote inflammation and invasion parameters through regulation of the AhR pathway.
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In summary, the epidemiological and biomonitoring studies suggest a potential association between exposure to chlorinated organic pesticides and increased risk of endometriosis; however, study limitations cannot exclude chance discovery owing to multiple comparisons, failure to adequately adjust for important confounders and lack of a dose–response relationship all weaken confidence in the link between COP exposure and endometriosis risk. A single tissue culture animal experiment conducted within the search window suggests that it is biologically plausible for COPs to promote endometriosis risk. Consequently, we suggest weak evidence linking exposure to COPs and endometriosis.
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3.3 Perfluoroalkyl and polyfluoroalkyl substances
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Perfluoroalkyl substances are a rather unique group of compounds due to their seemingly harmless properties. However, over the last decade, perfluoroalkyl and polyfluoroalkyl substances have been detected in blood and urine across the globe [47, 48]. Compromised of carbon-fluorine atoms, this extremely strong bond forms stable compounds that are used in clothing, cookware, carpets, and other common household items. Exposure to these compounds has been linked to adverse effects on metabolism, immune function, and fertility [49, 50, 51].
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In a case–control study [27], nine perfluorochemicals (PFCs) were measured in the blood of study participants by liquid chromatography–tandem mass spectrometry. Surgical visualization was used to confirm endometriosis in the operative population and MRI was used to confirm the absence of endometriosis in the control population. Both perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17–3.06]) and perfluorononanoic acid (PFNA) (2.20 [1.02–4.75]) were seen to be associated with endometriosis risk, where results were only moderately changed when adjusted for fecundity [27]. Patients with more severe stages of endometriosis (Stages III and IV) showed a higher concentration of perfluorooctane sulfonic acid (1.86 [1.05–3.30]) and PFOA (2.58 [1.18–5.64]) in their blood compared to controls [27]. Although this study shows a significant association between PFC exposure with an apparent dose response, there are a number of limitations to consider. First assignments of healthy study participants to the control population using MRI alone to exclude asymptomatic endometriosis cannot exclude women with endometriosis. Undiagnosed endometriosis was found in 45.3% of asymptomatic women undergoing laparoscopies for benign conditions [1] and thus the potential for misclassification error in this study weakens confidence in the purported association. Finally, circulating concentration of PFCs from the NHANES (2003–2006) study was compared in 753 women with self-reported diagnosis compared to healthy women without a diagnosis of endometriosis [52]. Results from this study showed that PFNA, PFOA, and perfluorooctane sulfonate (PFOS) were significantly higher among women with endometriosis compared to the control population. Women in the referent population of this study were significantly younger, non-Hispanic white, had more than one menstrual period in the last year and reported to be pregnant at the time of the exam. Furthermore, use of self-reported diagnosis of endometriosis may introduce group assignment bias and thus, these data must be interpreted with caution.
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The data linking exposure to Perfluoroalkyl substances and endometriosis are limited to the results of two biomonitoring studies. Although the results suggest that women with endometriosis have exposure to Perfluoroalkyl substances, any potential association with endometriosis is weak owing to limitations of these studies and absence of experimental animal studies or mechanistic experiments.
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3.4 Bisphenol A (BPA)
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A monomeric compound, bisphenol A (BPA) is used to polymerize plastics and can be found in common household items such as toilet paper, water bottles, the lining of tin cans, cash register receipts, dental sealants, and building supplies [53]. With over a million tons of BPA being used in the United States alone, BPA has become ubiquitous in the environment leading to widespread human exposure. BPA is able to bind to both estrogen receptors (Esr1 and Esr2), activate the estrogen signaling cascade and thus is considered a xenoestrogen [54]. Estrogenic capacity has led some to postulate that BPA exposure may play a role in the pathophysiology of endometriosis (Table 2).
Urinary BPA levels were found in all analyzed samples; with a statistically significant difference between patients and controls. Urinary BPA concentrations were significantly greater (p = 0.001) in women with endometriosis compared to the control group.
No statistically significant association between total urinary BPA concentrations and endometriosis overall. However, significant results were seen in urine in relation to non-ovarian pelvic endometriosis (2nd quartile vs. lowest quartile: OR = 3.0; 95% CI: 1.2–7.3 and 3rd vs. lowest quartile: OR = 3.0; 95% CI: 1.1–7.6), but not ovarian endometriosis.
BPA was found in 51.7% and BPB was found in sera 27.6% but either could not be detected in all the control cases. Suggests an association between at least one of the compound endometriosis risk.
No significant (p = 0.24) association of endometriosis with urinary BPA concentration.
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Table 2.
Summary of exposures and outcomes in epidemiological studies designed to investigate the association between Bisphenol A (BPA) exposure and endometriosis.
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A population-based case–control study [56], analyzed the urine from 143 women with confirmed or suspected endometriosis (cases) and 287 healthy controls. Urinary creatinine concentrations, age, reference year, as well as both ovarian and non-ovarian pelvic endometriosis were taken into account. Overall, the urinary BPA concentrations in cases did not differ from the control group. However, unconditional logistic regression analysis revealed that the second versus lowest quartile and third versus lowest quartile had increased adjusted odds ratio (aOR 3.0; 95% CI: 1.2–7.3 and aOR 3.0; 95% CI: 1.1–7.6) for higher BPA concentrations in women with non-ovarian pelvic endometriosis; however, there was no association between urine BPA concentrations and ovarian endometriosis. Moreover, there was no relationship between the highest urine concentrations of BPA and endometriosis overall as well as for non-ovarian pelvic endometriosis and ovarian endometriosis. Furthermore, the lack of a dose–response relationship with increasing urine concentrations of BPA weakens confidence in the potential link between BPA exposure and endometriosis risk.
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Results of biomonitoring studies revealed that mean BPA concentrations in the plasma of infertile women with endometriosis (n = 11), polycystic ovarian syndrome (PCOS, n = 31) and PCOS plus endometriosis (n = 3) combined (4.66 ± 3.52, 95% CI; 3.60–5.72 ng/ml) were significantly greater than in a control population (n = 34) of healthy fertile women (2.64 ± 3.99, 95% CI; 1.24–4.03 ng/ml) [59]. In women who reported a diagnosis of endometriosis, the mean ± (SD) concentration of BPA was 4.59 ± 1.22 ng/ml (range < LOQ – 5.31 ng/ml). Moreover, BPA concentrations were quantifiable in only 3% of study participants and comparisons with the fertile controls was not reported. Given the ubiquitous nature of BPA, the low detection frequency in this study is rather surprising and thus we interpret these findings with caution. The small sample size, self-reported diagnosis of endometriosis and associated potential for misclassification error are important limitations of this study. Results of a much larger cross-sectional study of 166 Japanese women [58], showed no significant difference in BPA levels in the urine. BPA concentrations were non-significantly (p = 0.24) greater in women with endometriosis stage 0–I (median = 0.74 μg/g after adjusting to creatinine levels), whereas women with stages II-IV endometriosis had a median concentration of 0.93 μg/g creatinine [58]. BPA levels measured in the sera from healthy fertile (n = 11) and endometriotic women (n = 58) found that both BPA and bisphenol B (BPB) levels were detectable in 51.7% and 27.6% of cases, respectively whereas the control patients showed a complete absence of both compounds [57]. Recently, urinary concentrations of BPA were significantly greater in women (n = 68) with endometriosis (1.17–12.68 pg/μl) compared to a control population (n = 60) (1.28–2.35 pg/μl) [55]. Finally, BPA has a short half-life and the measures in women with a diagnosis of endometriosis are temporally disconnected from the onset of disease which may have originated years earlier in time. The interval between onset of symptoms and diagnosis ranges from 6 to 12 years [34] and thus exposure measurements made after diagnosis are difficult to link with the development of endometriosis. Therefore, reverse causation cannot be excluded as a potential explanation for differences in circulating concentrations of the toxicants measured.
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In an animal study [60], BPA and bisphenol AF (BPAF) affected endometriosis lesion development in ovariectomized and hormonally intact mice specific to dose and hormonal status of the host mouse. Minced uterine tissue was injected into the peritoneal cavity of host mice. In this study, BPA treatment disrupted ovarian steroidogenic pathways resulting in lower progesterone levels and higher atretic oocyte numbers [60]. BPAF and BPA had higher epithelial proliferation scores, although this was only significant in the highest dose of 900 ppm. Both compounds mimicked estrogen, with BPAF having a stronger effect than estrogen [60]. Taken together, these data suggest that BPA and related compounds can affect mechanisms important in the pathophysiology of endometriosis. However, the concentrations of BPA needed to achieve these effects are higher than human exposure and thus are unlikely to be relevant at the concentrations of BPA measured in the general human population in contemporary studies.
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Results of a tissue culture experiments demonstrated that BPA treatment arrested human ESCs at the G2/M phase of the cell cycle, allowing for cell migration. Progesterone amplifying receptors such as insulin growth factor binding protein 1 and prolactin were also increased in response to BPA treatment [61]. These results suggest that BPA exposure could modulate endometrial stromal cells function; however, the effective concentrations exceed human exposure. Consequently, ambiguous study results from biomonitoring studies and lack of animal studies suggests a lack of association between BPA exposure and risk of endometriosis.
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3.5 Phthalate esters
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Phthalate esters are used as a softener in polyvinyl chloride plastics to make plastics flexible and can be found in products such as cosmetics, building materials, and in medical equipment such as intravenous bags, tubing and rubber stoppers in syringes and blood collection tubes. Phthalates leach from finished products leading to ubiquitous human exposure [62, 63]. Exposure to phthalate esters has been linked with decreased circulating testosterone [64] and animal experiments have shown that phthalates are competitive antagonists of the androgen receptor that displace testosterone from the receptor increasing its availability for conversion to estrogens via aromatase [65]. Therefore, it is postulated that exposure to phthalates could be associated with increased risk of endometriosis (Table 3).
Significantly higher plasma concentrations of MBzP (95% CI; 11.69–28.12 versus 3.34–8.10), BPA (95% CI; 3.60–5.72 versus 1.24–4.03), and MEHHP (95% CI; 5.10–8.43 versus 0.58–2.85).
Positive associations for MBP (OR = 1.36; 95% CI, 0.77–2.41) for the highest versus lowest three quartiles, and inverse associations for MEHP in relation to endometriosis (OR = 0.44; 95% CI, 0.19–1.02)
Greater urinary concentrations of MBzP and MEP in the urine of women with endometriosis compared to controls. Strong inverse association between urinary MEHP and endometriosis risk (aOR 0.3, 95% CI: 0.1–0.7).
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Table 3.
Summary of exposures and outcomes in epidemiological studies designed to investigate the association between phthalate exposure and endometriosis.
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A large case–control study [67], examined 626 women (495 cases; 131 controls) from 14 clinical centers. Study participants in both groups had a laparoscopy or a pelvic MRI to diagnose the presence of endometriosis. Among the 14 phthalate metabolites, mono-n-butyl phthalate, mono-[(2-carboxymethyl) hexyl] phthalate, mono (2-ethyl-5-carboxyphentyl) phthalate, mono (2-ethylhexyl) phthalate, mono (2-ethyl-5-hydroxyhexyl) phthalate, and mono (2-ethyl-5-oxohexyl), all showed two-fold significant increase in the odds of diagnosis. Results were adjusted for age, BMI, and creatinine. Depending on the method of diagnosis, monooctyl phthalate was restricted to surgical diagnosis of endometriosis with histological confirmation, whereas mono (2-ethylhexyl) phthalate was restricted to surgical diagnosis alone. However potential limitations may arise through adding concentrations as mECPP, mEHHP, mEOHP where all are metabolites of DEHP that were elevated in the operative cohort. Yet when summing DEHP metabolites (mECPP, mCMHP, mEHHP, mEOHP, and mEHP), there is a higher odds of endometriosis in the control population cohort. A further limitation is the lack of adjustment for multiple comparisons and thus chance discovery cannot be excluded. A large study from the National Health and Nutrition Examination Survey (NHANES, 1999–2004), examined phthalate levels in 1227 women, with a self-reported history of endometriosis and uterine leiomyomata. MEHP, monobutyl phthalate (MBP), monoethyl phthalate (MEP), and MBzP levels were measured in patients with each disease as well as patients that reported both [69]. Comparing the highest versus lowest three quartiles of urinary phthalate levels, MBP had an OR of 1.36 (95% CI, 0.77–2.41), MEHP was 0.44 (95% CI, 0.19–1.02), with no association for MEP and MBzP in endometriosis patients. Significantly higher plasma concentration of DBP which is broken down into MBP was also seen [69]. However, the use of self-reported cases may be unreliable. Contrary to the NHANES study, an increased endometriosis risk with an increase in urinary MBzP and MEP was described although the results were not significant [71]. Moreover, an inverse relationship between endometriosis risk and urinary MEHP was found (OR = 0.3; 95% CI = 0.1–0.7) and an inverse relationship was also suggested for DEHP, MEHHP, mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and ΣDEHP. Therefore, a compelling link between phthalate exposure and endometriosis has not been established.
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Results of several biomonitoring studies have documented higher concentrations of phthalate metabolites in the urine of women with endometriosis compared to a reference population. Plasma concentrations of mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were recently quantified by gas chromatography–mass spectrometry in infertile women with endometriosis (n = 11), polycystic ovarian syndrome (PCOS, n = 31) and PCOS plus endometriosis (n = 3) and 34 fertile women without evidence of gynecological disorders [59]. Overall, the mean (± SD) concentrations (ng/ml) of MBzP (19.9 ± 27.3 95% CI;11.69–28.12) and MEHHP (6.76 ± 5.54, 95% CI; 5.10–8.43) were significantly higher in infertile women compared to fertile women (5.72 ± 6.82, 95% CI; 3.34–8.10 and 1.71 ± 3.24, 0.58–2.85; respectively), whereas no differences were detected between groups for MMP and MEHP. The mean concentrations of MBzP and MEHHP in women with endometriosis were 40.9 ± 51.4 (range < LOQ – 116.5) and 5.43 ± 5.53 ng/ml (range < LOQ – 14.76), respectively. However, only 4–5% of women with endometriosis had concentrations of MBzP and MEHHP above the LOQ . Study participants were assigned to groups based upon self-reports of gynecological diagnoses which is open to misclassification error. In addition, the small sample size overall together with the limited number of study participants with quantifiable concentrations of phthalates are important limitations of this study.
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Recently, differences in serum DEHP concentrations were found between women with endometriosis and control patients using high-performance liquid chromatography [66]. The mean ± SD concentration of DEHP in cases (n = 50) was 65.3 ± 21.7 ng/ml, whereas it was undetectable in the controls. Among the four stages of the disease, women with endometriosis showed a linear increase in DEHP concentration with more advanced stages, although the sample size for stage I was n = 1. Age groups did not impact DEHP serum levels. Controversy remains, as DEHP is broken down by glutathione S-transferase and P450 enzyme, which has been reported to be compromised in endometriosis patients [72]. This may explain the difference in serum concentration, as the control patients are able to metabolize DEHP into metabolites which were not recorded. A further weakness of this study is the measurement of DEHP in the serum rather than metabolites in either the serum or urine and thus the potential for sample contamination cannot be discounted.
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A group from Taiwan investigated the association between GSTM1 polymorphisms and phthalates in adenomyosis, leiomyoma and endometriosis [68]. Although no relationship between the gene and the disease was found, there was an increase in urinary mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine, p < 0.05) among the 28 women with endometriosis relative to the 29 controls. In a subsequent study [70], the potential relationship between polymorphisms of CYP17A1 and phthalate exposure was explored in women with leiomyoma (fibroids, n = 36), endometriosis or adenomyosis (n = 44) and healthy controls (n = 69). However, only a marginally increased level of urinary MEHP was found in patients with endometriosis or adenomyosis [70].
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Our search failed to identify any experimental animal studies and only two mechanistic studies were located. MMP-2 and 9 activities, cellular invasiveness, Erk phosphorylation, and p21-activated kinase 4 expression (PAK4) were increased in endometrial stromal cell cultures exposed to DEHP [73]. All five significantly elevated markers play a role in cellular division, actin cytoskeletal dynamics, motility, cell survival, and immune defense [73, 74]. Another study found that DEHP treatment increased ESC reactive oxygen species (ROS) generation and decreased expression of superoxide dismutase (SOD), glutathione peroxidase (GPX), heme oxygenase (HO), and catalase (CAT). p-ERK/p-p38 and NF-κB were also increased [75]. This provides a potential explanation for the decreased expression of antioxidant enzymes and increased ROS. Lastly, Esr1 expression was also increase proportional to dose [75].
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In summary, while several studies revealed higher phthalate esters concentrations in women with endometriosis compared to controls the results of epidemiological studies remain equivocal. Moreover, the short half-life of 5–6 h for these chemicals suggests that higher concentrations detected in women with endometriosis compared to controls may be a consequence of the disease rather than a causal factor and thus reverse causation cannot be excluded. While in vitro studies suggest that phthalate esters can adversely affect mechanisms relevant to the pathophysiology of endometriosis, the effective concentrations are beyond human exposure and thus are unlikely to be clinically important.
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3.6 Metals
\n
Trace metals are nearly impossible to avoid in one’s lifetime, as they are found both naturally in our bodies and are produced during industrial processes. Exposure to metals has been reported to interfere with cell proliferation, migration, cell degeneration, oxidative stress, and apoptosis, nearly all of which are properties of endometriosis [76]. Therefore, a link between circulating concentrations of metals and endometriosis has been explored by several groups.
\n
A positive relationship between lead and endometriosis (adjusted OR = 2.59, 95% CI = 1.11–6.06) was found in Asian women whereas zinc levels were inversely associated with the disease (adjusted OR = 0.39, 95% CI = 0.18–0.88) [77]. While cadmium (Cd) levels were greater in women with endometriosis, the adjusted odds ratio was not significant [77]. Furthermore, no significant relationship was found between 20 trace elements quantified in the urine and three in blood [76]. Cases were surgically confirmed, whereas the controls were confirmed for the absence of endometriosis through MRI. Contrary to the findings by [24], Cd was inversely related to endometriosis risk, while urinary chromium and copper were marginally associated with endometriosis (aOR = 1.97; 95% CI: 1.21–3.19; aOR = 2.66; 95% CI: 1.26–5.64) [76]. Comparisons for each of the metals increase the probability of chance discovery and thus any association is considered suspect.
\n
Our search of the literature failed to reveal any recent animal studies; however, a tissue culture study revealed that Cd treatment-induced higher ESC proliferation (p = 0.02) in cultures derived from eutopic endometrium of women with endometriosis compared to controls [78]. Although the mechanism was not identified, it is suggested that Cd at 10−5 M is the toxic threshold for ESCs [78], a concentration that is orders of magnitude above typical human exposure.
\n
In summary, biomonitoring studies offer weak support for a potential link between metals exposure and endometriosis. Moreover, results from a tissue culture experiment suggest that Cd can adversely affect ESC proliferation but only at concentrations far in excess of human exposure. Consequently, we consider the evidence of a link between exposure to metals and risk of endometriosis to be speculative at best.
\n
\n
\n
\n
4. Future directions
\n
The current literature fails to provide compelling evidence for an association between exposure to environmental toxicants and endometriosis risk. Although current evidence is weak, involvement of environmental toxicants in the pathophysiology of endometriosis cannot be excluded. However, we propose that establishing a link between exposure to environmental toxicants and endometriosis is particularly challenging. Endometriosis is a heterogeneous disease in which peritoneal and ovarian endometriomas may arise by mechanisms that differ from DIE [79] and thus environmental interactions may be different from other forms of the disease.
\n
Absence of diagnostic tools such as a blood test for endometriosis together with normalization of pelvic pain and use of oral contraceptives among other factors leads to lengthy delays in diagnosis. Importantly, the interval between the onset and symptoms and definitive diagnosis of disease can be lengthy varying between 6 and 12 years [34]. Thus, there is a temporal disconnection between collection of biological samples for analysis and the onset of disease. Hence, the use of case–control studies may not permit convincing evidence of an association and the potential for reverse causation cannot be excluded.
\n
Identification of appropriate control groups poses an additional challenge since the prevalence of endometriosis in asymptomatic women can be high [1]. Furthermore, the hallmarks of endometriosis include chronic pelvic pain and infertility. Women dealing with chronic pain and or infertility may adopt activities or behaviors to reduce their pain or improve their chances of conceiving that diverge from the healthy fertile population and thus their exposures may be a function of disease status rather than factors contributing to the pathophysiology of endometriosis. Consequently, in the absence of clinical tools to diagnosis endometriosis, the most appropriate control group in the future may be symptomatic women undergoing laparoscopy with careful inspection of the pelvic cavity to exclude the presence of endometriosis, even though this step is admittedly imperfect [80].
\n
Epidemiological studies that adjust for potential confounders (e.g. age, BMI, parity, breast feeding, cigarette smoking, and alcohol consumption) and account for multiple comparisons could prove valuable in elucidating the role of exposure to environmental toxicants in the pathophysiology of endometriosis. Finally, it is unlikely that any group of women are exposed to a singly chemical or group of chemicals and thus quantification of chemicals from different chemical groups in a single study with an appropriate control, control for confounds and correction for multiple comparisons could prove informative.
\n
In the absences of robust epidemiological data experimental animal studies take on greater importance for establishing biological plausibility of a potential association. In general, there is a paucity of literature addressing the potential hazards of environmental toxicants in the survival and growth of endometriotic implants in animal models of endometriosis. While spontaneous endometriosis is predominately limited to humans and some non-human primates, animal xenotransplant models using dispersed cells from ectopic implants in women with endometriosis can provide valuable insight into potential chemical hazards relevant to endometriosis and mechanisms. However, dose levels used should include a concentration representative of human exposure. Similarly, tissue culture studies are essential for mechanistic insight; however, we propose that test concentrations should cover a range of doses that include concentrations below and representative of human exposure as well as high doses through to toxic levels.
\n
\n
\n
5. Summary and conclusions
\n
While in general, the epidemiological studies are judged to provide weak evidence of an association between exposure to environmental toxicants and endometriosis, a potential link cannot be excluded. Animal and cell culture models suggest biologically plausible mechanisms between the environmental toxicant exposures and endometriosis risk; however, the effective concentrations exceed human exposure levels. Consequently, we conclude that a causal relationship between exposure to any environmental toxicant and endometriosis does not currently exist, but the evidence does not allow us to exclude a potential link.
\n
\n\n',keywords:"endometriosis, endocrine disrupters, phthalates, bisphenol A, dioxin, estrogenic",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/70843.pdf",chapterXML:"https://mts.intechopen.com/source/xml/70843.xml",downloadPdfUrl:"/chapter/pdf-download/70843",previewPdfUrl:"/chapter/pdf-preview/70843",totalDownloads:765,totalViews:0,totalCrossrefCites:1,dateSubmitted:"October 22nd 2019",dateReviewed:"December 26th 2019",datePrePublished:"February 3rd 2020",datePublished:"January 14th 2021",dateFinished:"January 17th 2020",readingETA:"0",abstract:"Endometriosis is widely acknowledged to be an estrogen dependent disease or unknown etiology. Recognition that environmental toxicants can bind with and activate the estrogen receptor, dysregulate steroid metabolism and, in some cases, act as anti-androgenic substances (phthalate esters) has led to proposal that exposure to environmental toxicants are associated with increased risk of endometriosis. Since our last review of the subject in 2008, the literature has expanded with several epidemiological and biomonitoring studies suggesting a potential association, whereas others have been unable to demonstrate a link between exposure and enhanced risk. Therefore, we carried out a systematic review and critical appraisal of the literature published over the past decade (2009–2019). The majority of studies found dealt with exposure to polychlorinated biphenyls (PCBs), dioxins, dioxin-like and non-dioxin-like compounds, bisphenol A and phthalate esters. Several studies suggest a potential association between exposure to environmental toxicants; however, important weaknesses in study design, methodology, and analysis together with many contradictory studies weaken confidence in these associations. Consequently, we conclude that despite a growing literature, evidence for an association between exposure to environmental toxicants and risk of endometriosis remains weak.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/70843",risUrl:"/chapter/ris/70843",signatures:"Shay M. Freger and Warren G. Foster",book:{id:"9785",type:"book",title:"Endometriosis",subtitle:null,fullTitle:"Endometriosis",slug:"endometriosis",publishedDate:"January 14th 2021",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-465-0",printIsbn:"978-1-83962-464-3",pdfIsbn:"978-1-83962-466-7",isAvailableForWebshopOrdering:!0,editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Approach",level:"1"},{id:"sec_3",title:"3. Results",level:"1"},{id:"sec_3_2",title:"3.1 Polychlorinated biphenyls (PCBs), dioxin and dioxin-like compounds",level:"2"},{id:"sec_4_2",title:"3.2 Pesticides",level:"2"},{id:"sec_5_2",title:"3.3 Perfluoroalkyl and polyfluoroalkyl substances",level:"2"},{id:"sec_6_2",title:"3.4 Bisphenol A (BPA)",level:"2"},{id:"sec_7_2",title:"3.5 Phthalate esters",level:"2"},{id:"sec_8_2",title:"3.6 Metals",level:"2"},{id:"sec_10",title:"4. Future directions",level:"1"},{id:"sec_11",title:"5. Summary and conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'\nRawson JM. Prevalence of endometriosis in asymptomatic women. The Journal of Reproductive Medicine. 1991;36:513-515\n'},{id:"B2",body:'\nSampson J. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. American Journal of Obstetrics and Gynecology. 1927;14:422-469\n'},{id:"B3",body:'\nMatta K, Ploteau S, Coumoul X, Koual M, Le Bizec B, Antignac JP. et al. Associations between exposure to organochlorine chemicals and endometriosis in experimental studies: A systematic review protocol. Environment International. 2019;124:400-407\n'},{id:"B4",body:'\nMissmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. American Journal of Epidemiology. 2004;160:784-796\n'},{id:"B5",body:'\nUpson K, Sathyanarayana S, Scholes D, Holt VL. Early-life factors and endometriosis risk. Fertility and Sterility. 2015;104:964.e965-971.e965\n'},{id:"B6",body:'\nRier SE, Martin DC, Bowman RE, Dmowski WP, Becker JL. Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to tetrachlorodibenzo-p-dioxin. Fundamental and Applied Toxicology. 1993;21:433-441\n'},{id:"B7",body:'\nCano-Sancho G, Ploteau S, Matta K, Adoamnei E, Louis GB, Mendiola J, et al. Human epidemiological evidence about the associations between exposure to organochlorine chemicals and endometriosis: Systematic review and meta-analysis. Environment International. 2019;123:209-223\n'},{id:"B8",body:'\nLouis GM, Weiner JM, Whitcomb BW, Sperrazza R, Schisterman EF, Lobdell DT, et al. Environmental PCB exposure and risk of endometriosis. Human Reproduction. 2005;20:279-285\n'},{id:"B9",body:'\nPorpora MG, Ingelido AM, Domenico AD, Ferro A, Crobu M, Pallante D, et al. Increased levels of polychlorobiphenyls in Italian women with endometriosis. Chemosphere. 2005;63(8):1361-1367\n'},{id:"B10",body:'\nReddy BS, Rozati R, Reddy S, Kodampur S, Reddy P, Reddy R. High plasma concentrations of polychlorinated biphenyls and phthalate esters in women with endometriosis: A prospective case control study. Fertility and Sterility. 2006;85:775-779\n'},{id:"B11",body:'\nLebel G, Dodin S, Ayotte P, Marcoux S, Ferron LA, Dewailly E. Organochlorine exposure and the risk of endometriosis. Fertility and Sterility. 1998;69:221-228\n'},{id:"B12",body:'\nPauwels A, Schepens PJC, Hooghe TD, Delbeke L, Dhont M, Brouwer A, et al. The risk if endometriosis and exposure to dioxins and polychlorinated biphenyls: A case-control study of infertile women. Human Reproduction. 2001;16:2050-2055\n'},{id:"B13",body:'\nTsukino H, Hanaoka T, Sasaki H, Motoyama H, Hiroshima M, Tanaka T, et al. Associations between serum levels of selected organochlorine compounds and endometriosis in infertile Japanese women. Environmental Research. 2005;99:118-125\n'},{id:"B14",body:'\nAnger DL, Foster WG. The link between environmental toxicant exposure and endometriosis. Frontiers in Bioscience. 2008;13:1578-1593\n'},{id:"B15",body:'\nFoster WG, Agarwal SK. Environmental contaminants and dietary factors in endometriosis. Annals of the New York Academy of Sciences. 2002;955:213-229\n'},{id:"B16",body:'\nFoster WG. Do environmental contaminants adversely affect human reproductive physiology? Journal of Obstetrics and Gynaecology Canada. 2003;25:33-44\n'},{id:"B17",body:'\nFoster WG. Endocrine toxicants including 2,3,7,8-terachlorodibenzo-p-dioxin (TCDD) and dioxin-like chemicals and endometriosis: Is there a link? Journal of Toxicology and Environmental Health. Part B, Critical Reviews. 2008;11:177-187\n'},{id:"B18",body:'\nVabre P, Gatimel N, Moreau J, Gayrard V, Picard-Hagen N, Parinaud J, et al. Environmental pollutants, a possible etiology for premature ovarian insufficiency: A narrative review of animal and human data. Environmental Health. 2017;16:37\n'},{id:"B19",body:'\nFaroon O, Ruiz P. Polychlorinated biphenyls: New evidence from the last decade. Toxicology and Industrial Health. 2016;32:1825-1847\n'},{id:"B20",body:'\nBruner-Tran KL, Osteen KG. Dioxin-like PCBs and endometriosis. Systems Biology in Reproductive Medicine. 2010;56:132-146\n'},{id:"B21",body:'\nKorach KS, Sarver P, Chae K, McLachlan JA, McKinney JD. Estrogen receptor-binding activity of polychlorinated hydroxybiphenyls: Conformationally restricted structural probes. Molecular Pharmacology. 1988;33:120-126\n'},{id:"B22",body:'\nMoore M, Mustain M, Daniel K, Chen I, Safe S, Zacharewski T, et al. Antiestrogenic activity of hydroxylated polychlorinated biphenyl congeners identified in human serum. Toxicology and Applied Pharmacology. 1997;142:160-168\n'},{id:"B23",body:'\nPorpora MG, Medda E, Abballe A, Bolli S, De Angelis I, di Domenico A, et al. Endometriosis and organochlorinated environmental pollutants: A case-control study on Italian women of reproductive age. Environmental Health Perspectives. 2009;117:1070-1075\n'},{id:"B24",body:'\nCai LY, Izumi S, Suzuki T, Goya K, Nakamura E, Sugiyama T, et al. Dioxins in ascites and serum of women with endometriosis: A pilot study. Human Reproduction. 2010;26(1):117-126\n'},{id:"B25",body:'\nTrabert B, De Roos AJ, Schwartz SM, Peters U, Scholes D, Barr DB, et al. Non-dioxin-like polychlorinated biphenyls and risk of endometriosis. Environmental Health Perspectives. 2010;118:1280-1285\n'},{id:"B26",body:'\nPloteau S, Antignac JP, Volteau C, Marchand P, Vénisseau A, Vacher V, et al. Distribution of persistent organic pollutants in serum, omental, and parietal adipose tissue of French women with deep infiltrating endometriosis and circulating versus stored ratio as new marker of exposure. Environment International. 2016;97:125-136\n'},{id:"B27",body:'\nLouis GM, Peterson CM, Chen Z, Hediger ML, Croughan MS, Sundaram R, et al. Perfluorochemicals and endometriosis: The ENDO study. Epidemiology. 2012;23:799-805\n'},{id:"B28",body:'\nMartínez-Zamora MA, Mattioli L, Parera J, Abad E, Coloma JL, van Babel B, et al. Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis. Human Reproduction. 2015;30:1059-1068\n'},{id:"B29",body:'\nSimsa P, Mihalyi A, Schoeters G, Koppen G, Kyama CM, Den Hond EM, et al. Increased exposure to dioxin-like compounds is associated with endometriosis in a case-control study in women. Reproductive Biomedicine Online. 2010;20:681-688\n'},{id:"B30",body:'\nVichi S, Medda E, Ingelido AM, Ferro A, Resta S, Porpora MG, et al. Glutathione transferase polymorphisms and risk of endometriosis associated with polychlorinated biphenyls exposure in Italian women: A gene-environment interaction. Fertility and Sterility. 2012;97:1143-1151\n'},{id:"B31",body:'\nBuck Louis GM, Chen Z, Peterson CM, Hediger ML, Croughan MS, Sundaram R, et al. Persistent lipophilic environmental chemicals and endometriosis: The ENDO study. Environmental Health Perspectives. 2012;120:811-816\n'},{id:"B32",body:'\nMatsuzaka Y, Kikuti YY, Goya K, Suzuki T, Cai LY, Oka A, et al. Lack of an association human dioxin detoxification gene polymorphisms with endometriosis in Japanese women: Results of a pilot study. Environmental Health and Preventive Medicine. 2012;17:512-517\n'},{id:"B33",body:'\nSinaii N, Cleary SD, Younes N, Ballweg ML, Stratton P. Treatment utilization for endometriosis symptoms: A cross-sectional survey study of lifetime experience. Fertility and Sterility. 2007;87:1277-1286\n'},{id:"B34",body:'\nGreene R, Stratton P, Cleary SD, Ballweg ML, Sinaii N. Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertility and Sterility. 2009;91:32-39\n'},{id:"B35",body:'\nBruner-Tran KL, Ding T, Osteen KG. Dioxin and endometrial progesterone resistance. Seminars in Reproductive Medicine. 2010;28:59-68\n'},{id:"B36",body:'\nBruner-Tran KL, Rier SE, Eisenberg E, Osteen KG. The potential role of environmental toxins in the pathophysiology of endometriosis. Gynecologic and Obstetric Investigation. 1999;48(Suppl 1):45-56\n'},{id:"B37",body:'\nRier SE, Tuner WE, Martin DC, Morris R, Lucier GW, Clark GC. Serum levels of TCDD and dioxin-like chemicals in rhesus monkeys chronically exposed to dioxin: Correlation of increased serum PCB levels with endometriosis. Toxicological Sciences. 2001;59:147-159\n'},{id:"B38",body:'\nYang JZ, Agarwal SK, Foster WG. Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the pathophysiology of endometriosis in the Cynomolgus monkey. Toxicological Sciences. 2000;56:374-381\n'},{id:"B39",body:'\nHuang Q , Chen Y, Chen Q , Zhang H, Lin Y, Zhu M, et al. Dioxin-like rather than non-dioxin-like PCBs promote the development of endometriosis through stimulation of endocrine-inflammation interactions. Archives of Toxicology. 2017;91:1915-1924\n'},{id:"B40",body:'\nWang Y, Chen H, Wang N, Guo H, Fu Y, Xue S, et al. Combined 17β-estradiol with TCDD promotes M2 polarization of macrophages in the endometriotic milieu with aid of the interaction between endometrial stromal cells and macrophages. PLoS One. 2015;10:e0125559\n'},{id:"B41",body:'\nResuehr D, Glore DR, Taylor HS, Bruner-Tran KL, Osteen KG. Progesterone-dependent regulation of endometrial cannabinoid receptor type 1 (CB1-R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Fertility and Sterility. 2012;98:948.e941-956.e941\n'},{id:"B42",body:'\nWilling C, Peich M, Danescu A, Kehlen A, Fowler PA, Hombach-Klonisch S. Estrogen-independent actions of environmentally relevant AHR-agonists in human endometrial epithelial cells. Molecular Human Reproduction. 2011;17:115-126\n'},{id:"B43",body:'\nHu T, Yao M, Fu X, Chen C, Wu R. Polychlorinated biphenyl 104 promotes migration of endometrial stromal cells in endometriosis. Toxicology Letters. 2018;290:19-28\n'},{id:"B44",body:'\nCooney MA, Buck Louis GM, Hediger ML, Vexler A, Kostyniak PJ. Organochlorine pesticides and endometriosis. Reproductive Toxicology. 2010;30:365-369\n'},{id:"B45",body:'\nUpson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, et al. Organochlorine pesticides and risk of endometriosis: Findings from a population-based case-control study. Environmental Health Perspectives. 2013;121:1319-1324\n'},{id:"B46",body:'\nChiappini F, Bastón JI, Vaccarezza A, Singla JJ, Pontillo C, Miret N, et al. Enhanced cyclooxygenase-2 expression levels and metalloproteinase 2 and 9 activation by hexachlorobenzene in human endometrial stromal cells. Biochemical Pharmacology. 2016;109:91-104\n'},{id:"B47",body:'\nCalafat AM, Kuklenyik Z, Caudill SP, Reidy JA, Needham LL. Perfluorochemicals in pooled serum samples from United States residents in 2001 and 2002. Environmental Science & Technology. 2006;40:2128-2134\n'},{id:"B48",body:'\nGuruge KS, Taniyasu S, Yamashita N, Wijeratna S, Mohotti KM, Seneviratne HR, et al. Perfluorinated organic compounds in human blood serum and seminal plasma: A study of urban and rural tea worker populations in Sri Lanka. Journal of Environmental Monitoring. 2005;7:371-377\n'},{id:"B49",body:'\nBach CC, Vested A, Jørgensen KT, Bonde JP, Henriksen TB, Toft G. Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: A systematic review. Critical Reviews in Toxicology. 2016;46:735-755\n'},{id:"B50",body:'\nKielsen K, Shamim Z, Ryder LP, Nielsen F, Grandjean P, Budtz-Jørgensen E, et al. Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates. Journal of Immunotoxicology. 2016;13:270-273\n'},{id:"B51",body:'\nLiu G, Dhana K, Furtado JD, Rood J, Zong G, Liang L, et al. Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: A prospective study. PLoS Medicine. 2018;15:e1002502\n'},{id:"B52",body:'\nCampbell S, Raza M, Pollack AZ. Perfluoroalkyl substances and endometriosis in us women in NHANES 2003-2006. Reproductive Toxicology. 2016;65:230-235\n'},{id:"B53",body:'\nRashtian J, Chavkin DE, Merhi Z. Water and soil pollution as determinant of water and food quality/contamination and its impact on female fertility. Reproductive Biology and Endocrinology. 2019;17:5\n'},{id:"B54",body:'\nRochester JR. Bisphenol a and human health: A review of the literature. Reproductive Toxicology. 2013;42:132-155\n'},{id:"B55",body:'\nItoh H, Iwasaki M, Hanaoka T, Sasaki H, Tanaka T, Tsugane S. Urinary phthalate monoesters and endometriosis in infertile Japanese women. Science of the Total Environment. 2009;408:37-42\n'},{id:"B56",body:'\nUpson K, Sathyanarayana S, De Roos AJ, Koch HM, Scholes D, Holt VL. A population-based case-control study of urinary bisphenol A concentrations and risk of endometriosis. Human Reproduction. 2014;29:2457-2464\n'},{id:"B57",body:'\nCobellis L, Colacurci N, Trabucco E, Carpentiero C, Grumetto L. Measurement of bisphenol A and bisphenol B levels in human blood sera from healthy and endometriotic women. Biomedical Chromatography. 2009;23:1186-1190\n'},{id:"B58",body:'\nItoh H, Iwasaki M, Hanaoka T, Sasaki H, Tanaka T, Tsugane S. Urinary bisphenol-A concentration in infertile Japanese women and its association with endometriosis: A cross-sectional study. Environmental Health and Preventive Medicine. 2007;12:258-264\n'},{id:"B59",body:'\nPednekar PP, Gajbhiye RK, Patil AD, Surve SV, Datar AG, Balsarkar GD, et al. Estimation of plasma levels of bisphenol-A & phthalates in fertile & infertile women by gas chromatography-mass spectrometry. The Indian Journal of Medical Research. 2018;148:734-742\n'},{id:"B60",body:'\nJones RL, Lang SA, Kendziorski JA, Greene AD, Burns KA. Use of a mouse model of experimentally induced endometriosis to evaluate and compare the effects of bisphenol A and bisphenol AF exposure. Environmental Health Perspectives. 2018;126:127004\n'},{id:"B61",body:'\nForte M, Mita L, Cobellis L, Merafina V, Specchio R, Rossi S, et al. Triclosan and bisphenol A affect decidualization of human endometrial stromal cells. Molecular and Cellular Endocrinology. 2016;422:74-83\n'},{id:"B62",body:'\nSilva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, et al. Urinary levels of seven phthalate metabolites in the U.S. population from the national health and nutrition examination survey (NHANES) 1999-2000. Environmental Health Perspectives. 2004;112:331-338\n'},{id:"B63",body:'\nTyrrell J, Melzer D, Henley W, Galloway TS, Osborne NJ. Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010. Environment International. 2013;59:328-335\n'},{id:"B64",body:'\nMeeker JD, Ferguson KK. Urinary phthalate metabolites are associated with decreased serum testosterone in men, women, and children from NHANES 2011-2012. The Journal of Clinical Endocrinology and Metabolism. 2014;99(11):4346-4352\n'},{id:"B65",body:'\nLague E, Tremblay JJ. Antagonistic effects of testosterone and the endocrine disruptor mono-(2-ethylhexyl) phthalate on INSL3 transcription in Leydig cells. Endocrinology. 2008;149:4688-4694\n'},{id:"B66",body:'\nNazir S, Usman Z, Imran M, Lone KP, Ahmad G. Women diagnosed with endometriosis show high serum levels of diethyl hexyl phthalate. Journal of Human Reproductive Sciences. 2018;11:131-136\n'},{id:"B67",body:'\nBuck Louis GM, Peterson CM, Chen Z, Croughan M, Sundaram R, Stanford J, et al. Bisphenol A and phthalates and endometriosis: The endometriosis: Natural history, diagnosis and outcomes study. Fertility and Sterility. 2013;100:162-169\n'},{id:"B68",body:'\nHuang PC, Tsai EM, Li WF, Liao PC, Chung MC, Wang YH, et al. Association between phthalate exposure and glutathione S-transferase M1 polymorphism in adenomyosis, leiomyoma and endometriosis. Human Reproduction. 2010;25:986-994\n'},{id:"B69",body:'\nWeuve J, Hauser R, Calafat AM, Missmer SA, Wise LA. Association of exposure to phthalates with endometriosis and uterine leiomyomata: Findings from NHANES, 1999-2004. Environmental Health Perspectives. 2010;118:825-832\n'},{id:"B70",body:'\nHuang PC, Li WF, Liao PC, Sun CW, Tsai EM, Wang SL. Risk for estrogen-dependent diseases in relation to phthalate exposure and polymorphisms of CYP17A1 and estrogen receptor genes. Environmental Science and Pollution Research International. 2014;21:13964-13973\n'},{id:"B71",body:'\nUpson K, Sathyanarayana S, De Roos AJ, Thompson ML, Scholes D, Dills R, et al. Phthalates and risk of endometriosis. Environmental Research. 2013;126:91-97\n'},{id:"B72",body:'\nKubiszeski EH, de Medeiros SF, da Silva Seidel JA, Barbosa JS, Galera MF, Galera BB. Glutathione s-transferase M1 and T1 gene polymorphisms in Brazilian women with endometriosis. Journal of Assisted Reproduction and Genetics. 2015;32:1531-1535\n'},{id:"B73",body:'\nKim SH, Cho S, Ihm HJ, Oh YS, Heo SH, Chun S, et al. Possible role of phthalate in the pathogenesis of endometriosis: In vitro, animal, and human data. The Journal of Clinical Endocrinology and Metabolism. 2015;100:E1502-E1511\n'},{id:"B74",body:'\nDart AE, Wells CM. P21-activated kinase 4—Not just one of the PAK. European Journal of Cell Biology. 2013;92:129-138\n'},{id:"B75",body:'\nCho YJ, Park SB, Han M. Di-(2-ethylhexyl)-phthalate induces oxidative stress in human endometrial stromal cells in vitro. Molecular and Cellular Endocrinology. 2015;407:9-17\n'},{id:"B76",body:'\nPollack AZ, Louis GM, Chen Z, Peterson CM, Sundaram R, Croughan MS, et al. Trace elements and endometriosis: The ENDO study. Reproductive Toxicology. 2013;42:41-48\n'},{id:"B77",body:'\nLai GL, Yeh CC, Yeh CY, Chen RY, Fu CL, Chen CH, et al. Decreased zinc and increased lead blood levels are associated with endometriosis in Asian women. Reproductive Toxicology. 2017;74:77-84\n'},{id:"B78",body:'\nSilva N, Tennekoon K, Senanayake H, Samarakoon S. Metalloestrogen cadmium stimulates proliferation of stromal cells derived from the eutopic endometrium of women with endometriosis. Taiwanese Journal of Obstetrics & Gynecology. 2013;52:540-545\n'},{id:"B79",body:'\nGordts S, Koninckx P, Brosens I. Pathogenesis of deep endometriosis. Fertility and Sterility. 2017;108:872.e871-885.e871\n'},{id:"B80",body:'\nWykes CB, Clark TJ, Khan KS. Accuracy of laparoscopy in the diagnosis of endometriosis: A systematic quantitative review. BJOG. 2004;111:1204-1212\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Shay M. Freger",address:null,affiliation:'
Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
'},{corresp:"yes",contributorFullName:"Warren G. Foster",address:"fosterw@mcmaster.ca",affiliation:'
Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
'}],corrections:null},book:{id:"9785",type:"book",title:"Endometriosis",subtitle:null,fullTitle:"Endometriosis",slug:"endometriosis",publishedDate:"January 14th 2021",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-465-0",printIsbn:"978-1-83962-464-3",pdfIsbn:"978-1-83962-466-7",isAvailableForWebshopOrdering:!0,editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"426919",title:"MSc.",name:"Mojca",middleName:null,surname:"Ravnikar Turk",email:"mojca.turk@zag.si",fullName:"Mojca Ravnikar Turk",slug:"mojca-ravnikar-turk",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"Slovenian National Building and Civil Engineering Institute",institutionURL:null,country:{name:"Slovenia"}}},booksEdited:[],chaptersAuthored:[{id:"77939",title:"Rejuvenator Obtained by Pyrolysis of Waste Tires for Use in Asphalt Mixtures with Added Reclaimed Asphalt",slug:"rejuvenator-obtained-by-pyrolysis-of-waste-tires-for-use-in-asphalt-mixtures-with-added-reclaimed-as",abstract:"Although in recent years, big progress has been made in the field of recovering waste tires, they still represent an unwanted waste and their production is constantly increasing. We can use waste tires as a raw material for a new product. In our study, multiple liquid products were produced by pyrolysis of waste tires. After extensive testing of their properties, we selected the most suitable pyrolytic product for the purpose of rejuvenation. Rejuvenators are designed to soften the old, brittle and stiff aged bitumen in reclaimed asphalt. Bitumen with its viscoelastic characteristics is the most important component of asphalt and dictates its behaviour. Commonly bitumen, after adding rejuvenator, becomes less viscous, more ductile and its coating properties are restored. By using a pyrolytic rejuvenator, the proportion of reclaimed asphalt added to the asphalt mixture was increased. The reuse of reclaimed asphalt and waste tires means a reduction in waste material and is therefore important for the preservation of the environment and sustainable development.",signatures:"Lidija Ržek, Mojca Ravnikar Turk and Marjan Tušar",authors:[{id:"420336",title:"Dr.",name:"Lidija",surname:"Ržek",fullName:"Lidija Ržek",slug:"lidija-rzek",email:"lidija.rzek@zag.si"},{id:"426919",title:"MSc.",name:"Mojca",surname:"Ravnikar Turk",fullName:"Mojca Ravnikar Turk",slug:"mojca-ravnikar-turk",email:"mojca.turk@zag.si"},{id:"426922",title:"Dr.",name:"Marjan",surname:"Tušar",fullName:"Marjan Tušar",slug:"marjan-tusar",email:"marjan.tusar@ki.si"}],book:{id:"10862",title:"Recent Perspectives in Pyrolysis Research",slug:"recent-perspectives-in-pyrolysis-research",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"207156",title:"Dr.",name:"Asfaw",surname:"Gezae Daful",slug:"asfaw-gezae-daful",fullName:"Asfaw Gezae Daful",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"316360",title:"Dr.",name:"Jorge",surname:"Reyes-Rivera",slug:"jorge-reyes-rivera",fullName:"Jorge Reyes-Rivera",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/316360/images/system/316360.jpg",biography:"Dr. Jorge Reyes-Rivera has worked during the last fifteen years studying the ontogeny, anatomy, gene expression, structural chemical composition, evolution and systematics in succulent plants, mainly in the Cactaceae family. He is a member of the National System of Researchers (SNI-CONACyT) in Mexico. The results of his research work have been published in several scientific articles in JCR journals as well as in book chapters. His most recent work focuses on the study of gene expression in the cambial zone, the structural chemical characterization of internal and external lignocellulosic organs and their relationship to the taxonomy and evolution of species in Cactaceae. He is currently performing a postdoctoral research in the Universidad Nacional Autónoma de México on the chemotaxonomy of different species of Cactaceae using the spines of the stem.",institutionString:"Universidad Nacional Autónoma de México",institution:{name:"National Autonomous University of Mexico",institutionURL:null,country:{name:"Mexico"}}},{id:"420336",title:"Dr.",name:"Lidija",surname:"Ržek",slug:"lidija-rzek",fullName:"Lidija Ržek",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"421523",title:"Dr.",name:"Meegalla R.",surname:"Chandraratne",slug:"meegalla-r.-chandraratne",fullName:"Meegalla R. Chandraratne",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},{id:"421524",title:"Dr.",name:"Marie",surname:"Loridon",slug:"marie-loridon",fullName:"Marie Loridon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Higher Colleges of Technology",institutionURL:null,country:{name:"United Arab Emirates"}}},{id:"422096",title:"Ph.D. Student",name:"Deodatus",surname:"Kazawadi",slug:"deodatus-kazawadi",fullName:"Deodatus Kazawadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"422546",title:"Dr.",name:"Jin",surname:"Hu",slug:"jin-hu",fullName:"Jin Hu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"424982",title:"Prof.",name:"Justin",surname:"Ntalikwa",slug:"justin-ntalikwa",fullName:"Justin Ntalikwa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"424983",title:"Dr.",name:"Godlisten",surname:"Kombe",slug:"godlisten-kombe",fullName:"Godlisten Kombe",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"426922",title:"Dr.",name:"Marjan",surname:"Tušar",slug:"marjan-tusar",fullName:"Marjan Tušar",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Institute of Chemistry",institutionURL:null,country:{name:"Slovenia"}}}]},generic:{page:{slug:"retraction-and-correction-policy",title:"Retraction and Correction Policy",intro:"
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
",metaTitle:"Retraction and Correction Policy",metaDescription:"Retraction and Correction Policy",metaKeywords:null,canonicalURL:"/page/retraction-and-correction-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"
IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\\n\\n
1. RETRACTIONS
\\n\\n
A Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\n
A formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\\n\\n
\\n\\t
Data fabrication
\\n\\t
Data recycling in a purportedly original research article
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Severe plagiarism - whether or not the plagiarism is to be deemed severe will be determined by the Academic Editor and verified by plagiarism checking software
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Double publication
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Copyright infringement - for example, if a Chapter uses copyrighted figures without permission.
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Unreliable findings
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Unethical research practices
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Any other practice or act considered potentially harmful to the scientific community.
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Publishing of a Retraction Notice will adhere to the following guidelines:
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All relevant bibliographic information about a retracted Chapter will be given in the title.
\\n\\t
A Retraction Notice will be published as a regular book Chapter and will be given its own Chapter number.
\\n\\n\\n
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Authors shall be required to approve a proposed retraction of their Chapter. If Authors maintain that their Chapter should not be retracted, the Academic Editor may issue a Statement of Concern (see 2. below).
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\\n\\n
1.2. REMOVALS AND CANCELLATIONS
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\\n\\t
Additionally, a Chapter retracted on grounds of copyright infringement (e.g. double publication) may be Removed by the publisher should the original copyright owner request such action. A Chapter retracted on grounds of its potential to harm the scientific community, for example, when a Chapter is defamatory in nature, may also be subject to removal.
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No formal Removal Notice will be published but a notice citing the reason for removal will be prominently displayed in place of a retracted and subsequently removed Chapter.
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Chapters published due to inadvertent production mistakes shall be canceled and the cancellation notice will be published.
\\n
\\n\\n
2. STATEMENTS OF CONCERN
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A Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
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\\n\\t
Authors refuse to approve a retraction proposed by the Academic Editor
\\n\\t
There is inconclusive evidence of scientific misconduct
\\n\\t
Authors and their respective institutions fail or refuse to provide adequate assistance in an investigation
\\n\\t
The publication of a Statement of Concern will adhere to the Retraction Notice guidelines outlined above
\\n\\t
An article PDF for which a Statement of Concern is published will remain available online without being edited or watermarked
\\n
\\n\\n
IntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n
3. CORRECTIONS
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A Correction will be issued by the Academic Editor when:
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Only a small portion of a Chapter is flawed in a way that does not severely affect any findings.
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It is determined that the scientific community would be better served by a Correction rather than a Retraction.
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Corrections will be issued in one of two distinct forms -- ERRATUM or CORRIGENDUM, depending on the origin of a mistake.
\\n
\\n\\n
3.1. ERRATUM
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An Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
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A published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
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3.2. CORRIGENDUM
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A Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
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4. FINAL REMARKS
\\n\\n
IntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\n
In the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\n
The general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n
1. RETRACTIONS
\n\n
A Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\n
A formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\n
\n\t
Data fabrication
\n\t
Data recycling in a purportedly original research article
\n\t
Severe plagiarism - whether or not the plagiarism is to be deemed severe will be determined by the Academic Editor and verified by plagiarism checking software
\n\t
Double publication
\n\t
Copyright infringement - for example, if a Chapter uses copyrighted figures without permission.
\n\t
Unreliable findings
\n\t
Unethical research practices
\n\t
Any other practice or act considered potentially harmful to the scientific community.
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\n\n
Publishing of a Retraction Notice will adhere to the following guidelines:
\n\n\n\t
All relevant bibliographic information about a retracted Chapter will be given in the title.
\n\t
A Retraction Notice will be published as a regular book Chapter and will be given its own Chapter number.
\n\n\n
\n\t
Authors shall be required to approve a proposed retraction of their Chapter. If Authors maintain that their Chapter should not be retracted, the Academic Editor may issue a Statement of Concern (see 2. below).
\n
\n\n
1.2. REMOVALS AND CANCELLATIONS
\n\n
\n\t
Additionally, a Chapter retracted on grounds of copyright infringement (e.g. double publication) may be Removed by the publisher should the original copyright owner request such action. A Chapter retracted on grounds of its potential to harm the scientific community, for example, when a Chapter is defamatory in nature, may also be subject to removal.
\n\t
No formal Removal Notice will be published but a notice citing the reason for removal will be prominently displayed in place of a retracted and subsequently removed Chapter.
\n\t
Chapters published due to inadvertent production mistakes shall be canceled and the cancellation notice will be published.
\n
\n\n
2. STATEMENTS OF CONCERN
\n\n
A Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\n
\n\t
Authors refuse to approve a retraction proposed by the Academic Editor
\n\t
There is inconclusive evidence of scientific misconduct
\n\t
Authors and their respective institutions fail or refuse to provide adequate assistance in an investigation
\n\t
The publication of a Statement of Concern will adhere to the Retraction Notice guidelines outlined above
\n\t
An article PDF for which a Statement of Concern is published will remain available online without being edited or watermarked
\n
\n\n
IntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n
3. CORRECTIONS
\n\n
A Correction will be issued by the Academic Editor when:
\n\n
\n\t
Only a small portion of a Chapter is flawed in a way that does not severely affect any findings.
\n\t
It is determined that the scientific community would be better served by a Correction rather than a Retraction.
\n\t
Corrections will be issued in one of two distinct forms -- ERRATUM or CORRIGENDUM, depending on the origin of a mistake.
\n
\n\n
3.1. ERRATUM
\n\n
An Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\n
A published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n
3.2. CORRIGENDUM
\n\n
A Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n
4. FINAL REMARKS
\n\n
IntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\n
In the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\n
The general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
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I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). 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On a regional scale, this contribution can be even more significant for many coastal regions. In this chapter, we show that dynamics of small river plumes is significantly different from that of plumes generated by large rivers. Spatial structure of small plumes is generally characterized by sharper horizontal and vertical gradients. As a result, small plumes exhibit more energetic temporal variability in response to external forcing. In this chapter, we address several dynamical features typical for small plumes. We describe and discuss the response of small plumes to wind forcing and river discharge variability, the interaction between neighboring small plumes, and the generation of high-frequency internal waves in coastal ocean by small rivers. We also substantiate the Lagrangian approach to numerical modeling of small river plumes.",book:{id:"8007",slug:"estuaries-and-coastal-zones-dynamics-and-response-to-environmental-changes",title:"Estuaries and Coastal Zones",fullTitle:"Estuaries and Coastal Zones - Dynamics and Response to Environmental Changes"},signatures:"Alexander Osadchiev and Peter Zavialov",authors:[{id:"296909",title:"Prof.",name:"Peter",middleName:null,surname:"Zavialov",slug:"peter-zavialov",fullName:"Peter Zavialov"},{id:"296910",title:"Dr.",name:"Alexander",middleName:null,surname:"Osadchiev",slug:"alexander-osadchiev",fullName:"Alexander Osadchiev"}]},{id:"41072",doi:"10.5772/51864",title:"The November, 1st, 1755 Tsunami in Morocco: Can Numerical Modeling Clarify the Uncertainties of Historical Reports?",slug:"the-november-1st-1755-tsunami-in-morocco-can-numerical-modeling-clarify-the-uncertainties-of-histori",totalDownloads:2398,totalCrossrefCites:4,totalDimensionsCites:10,abstract:null,book:{id:"2221",slug:"tsunami-analysis-of-a-hazard-from-physical-interpretation-to-human-impact",title:"Tsunami - Analysis of a Hazard",fullTitle:"Tsunami - Analysis of a Hazard - From Physical Interpretation to Human Impact"},signatures:"R. Omira, M.A. Baptista, S. Mellas, F. Leone, N. Meschinet de Richemond, B. Zourarah and J-P. Cherel",authors:[{id:"16693",title:"Prof.",name:"Maria Ana",middleName:null,surname:"Baptista",slug:"maria-ana-baptista",fullName:"Maria Ana Baptista"},{id:"16695",title:"Dr.",name:"Rachid",middleName:null,surname:"Omira",slug:"rachid-omira",fullName:"Rachid Omira"},{id:"92702",title:"Prof.",name:"Frederic",middleName:null,surname:"Leone",slug:"frederic-leone",fullName:"Frederic Leone"},{id:"148352",title:"MSc.",name:"Samira",middleName:null,surname:"Mellas",slug:"samira-mellas",fullName:"Samira Mellas"},{id:"148353",title:"Prof.",name:"Bendahou",middleName:null,surname:"Zourarah",slug:"bendahou-zourarah",fullName:"Bendahou Zourarah"},{id:"148356",title:"Prof.",name:"Jean-Philippe",middleName:null,surname:"Cherel",slug:"jean-philippe-cherel",fullName:"Jean-Philippe Cherel"},{id:"157593",title:"Prof.",name:"Nancy",middleName:null,surname:"Meschinet De Richemond",slug:"nancy-meschinet-de-richemond",fullName:"Nancy Meschinet De Richemond"}]},{id:"58729",doi:"10.5772/intechopen.73217",title:"Spatio-Temporal Analysis of Sea Surface Temperature in the East China Sea Using TERRA/MODIS Products Data",slug:"spatio-temporal-analysis-of-sea-surface-temperature-in-the-east-china-sea-using-terra-modis-products",totalDownloads:1044,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"Sea surface temperature (SST) is an important parameter in determining the atmospheric and oceanic circulations, and satellite thermal infrared remote sensing can obtain the SST with very high spatio-temporal resolutions. The study first validated the accuracy of TERRA MODIS SST daytime and nighttime products with the timing SST measurements from the ships in the East China Sea (ECS) in February, May, August and November, 2001, and then the daily variation of daytime and nighttime SST difference was analyzed. Using 16-year MODIS SST monthly products data from February 2000 to January 2016, when all SST monthly products in February, May, August and November were averaged respectively, the seasonal spatial distribution pattern of SST in the ECS was discovered. After monthly sea surface temperature anomaly was finally processed by the empirical orthogonal function (EOF), the interannual variability of SST in the ECS was discussed. The results show that the MODIS SST daily products have a good accuracy with a mean absolute percentage error (MAPE) below 5%. The SST difference between day and night is the largest in winter, followed by spring, then for autumn and the smallest in summer, while the diurnal SST difference is very low for the same season in the different seas. The SST in the ECS displays the obvious seasonal spatial distribution pattern, in which the SST of winter is gradually increasing from north to south, while local temperature difference is the largest for 26.5°C in a year. In comparison, the SST in summer tends uniform and the difference is not more than 5°C in the whole sea. From the EOF analysis of SST anomaly, the interannual variability of SST in the ECS is affected by the East Asian monsoon, the latitudinal difference of solar radiation, the offshore circulation and the submarine terrain.",book:{id:"6195",slug:"sea-level-rise-and-coastal-infrastructure",title:"Sea Level Rise and Coastal Infrastructure",fullTitle:"Sea Level Rise and Coastal Infrastructure"},signatures:"Shaoqi Gong and Kapo Wong",authors:[{id:"219135",title:"Dr.",name:"Shaoqi",middleName:null,surname:"Gong",slug:"shaoqi-gong",fullName:"Shaoqi Gong"},{id:"219138",title:"Mr.",name:"Wong",middleName:null,surname:"Kapo",slug:"wong-kapo",fullName:"Wong Kapo"}]},{id:"63609",doi:"10.5772/intechopen.80903",title:"Saltwater Intrusion in the Changjiang Estuary",slug:"saltwater-intrusion-in-the-changjiang-estuary",totalDownloads:1440,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Saltwater intrusion in the Changjiang Estuary and the impacts of river discharge, tide, wind, sea level rise, river basin, and major estuary projects on saltwater intrusion are studied in this chapter. There is a net landward flow in the NB (North Branch) when river discharge is low during spring tide, resulting in a type of saltwater intrusion known as the SSO (saltwater-spilling-over from the NB into the SB (South Branch)), which is the most striking characteristic of saltwater intrusion in the estuary. A three-dimension numerical model with HSIMT-TVD advection scheme was developed to study the hydrodynamic processes and saltwater intrusion in the Changjiang Estuary. Saltwater intrusion in the estuary is controlled mainly by river discharge and tide, but is also influenced by wind, sea level rise, river basin, and estuary projects. Saltwater intrusion is enhanced when river discharge decreases. There is more time for the reservoir to take freshwater from the river when river discharge is larger. The fortnightly spring tide generates greater saltwater intrusion than the neap tide. The saltwater intrusion in the SP (South Passage) is stronger than that in the NP (North Passage), and the intrusion in the NP is stronger than that in the NC (North Channel). The northerly wind produces southward currents along the Subei coast as well as the landward Ekman transport, which enhances the saltwater intrusion in the NC and NB and weakens the saltwater intrusion in the NP and SP. Saltwater intrusion becomes stronger as the sea level rises and is much stronger when river discharge is much small. The DWP (Deep Waterway Project) alleviates the saltwater intrusion in the NC and the lower reaches of the NP and enhances the saltwater intrusion in the SP and in the upper reaches of the NP. The Three Gorges Dam (TGD) increases river discharge in winter, which weakens saltwater intrusion, and is favorable for reducing the burden of freshwater supplement in the highly populated estuarine region. The Water Diversion South to the North Project (WDP) decreases river discharge, enhances saltwater intrusion, and is unfavorable for freshwater supply in the estuary.",book:{id:"8669",slug:"coastal-environment-disaster-and-infrastructure-a-case-study-of-china-s-coastline",title:"Coastal Environment, Disaster, and Infrastructure",fullTitle:"Coastal Environment, Disaster, and Infrastructure - A Case Study of China's Coastline"},signatures:"Jianrong Zhu, Hui Wu, Lu Li and Cheng Qiu",authors:[{id:"266207",title:"Dr.",name:"Jianrong",middleName:null,surname:"Zhu",slug:"jianrong-zhu",fullName:"Jianrong Zhu"}]}],mostDownloadedChaptersLast30Days:[{id:"70994",title:"Circulations in the Pearl River Estuary: Observation and Modeling",slug:"circulations-in-the-pearl-river-estuary-observation-and-modeling",totalDownloads:779,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"This chapter reports a cruise survey on the Pearl River Estuary (PRE) and adjacent costal water in the period between May 3, 2014 and May 11, 2014. The circulation and salinity structure were sampled for different tidal phases. With the cruise data, a “sandwich” structure of the lateral salinity distribution and a two-layer structure of longitudinal circulation were identified, together with high variations influenced by wind and tide. Furthermore, longitudinally orientated convergence or divergence of the lateral velocity close to the channel location for certain tidal conditions was observed. The finite volume community ocean model (FVCOM) is configured and run with high spatial resolution of 100 m in the PRE. An atmospheric model, the Weather Research and Forecasting (WRF) Model, is also run to provide high spatial and temporal resolution of atmospheric forcing for the FVCOM. The FVCOM modeling skill assessment is conducted using the cruise salinity and velocity data, as well as water levels, showing that the model can well simulate the velocity and salinity structures. The numerical model reveals that there is a strong neap-spring cycle for the PRE de-tided circulation with 0.37 m s−1 during the neap tide about 42% stronger than that (0.26 m s−1) during the spring tide in the surface layer.",book:{id:"8007",slug:"estuaries-and-coastal-zones-dynamics-and-response-to-environmental-changes",title:"Estuaries and Coastal Zones",fullTitle:"Estuaries and Coastal Zones - Dynamics and Response to Environmental Changes"},signatures:"Jiayi Pan, Wenfeng Lai and Adam Thomas Devlin",authors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"},{id:"302219",title:"Associate Prof.",name:"Jiayi",middleName:null,surname:"Pan",slug:"jiayi-pan",fullName:"Jiayi Pan"},{id:"309888",title:"Dr.",name:"Wenfeng",middleName:null,surname:"Lai",slug:"wenfeng-lai",fullName:"Wenfeng Lai"}]},{id:"41072",title:"The November, 1st, 1755 Tsunami in Morocco: Can Numerical Modeling Clarify the Uncertainties of Historical Reports?",slug:"the-november-1st-1755-tsunami-in-morocco-can-numerical-modeling-clarify-the-uncertainties-of-histori",totalDownloads:2398,totalCrossrefCites:4,totalDimensionsCites:10,abstract:null,book:{id:"2221",slug:"tsunami-analysis-of-a-hazard-from-physical-interpretation-to-human-impact",title:"Tsunami - Analysis of a Hazard",fullTitle:"Tsunami - Analysis of a Hazard - From Physical Interpretation to Human Impact"},signatures:"R. Omira, M.A. Baptista, S. Mellas, F. Leone, N. Meschinet de Richemond, B. Zourarah and J-P. Cherel",authors:[{id:"16693",title:"Prof.",name:"Maria Ana",middleName:null,surname:"Baptista",slug:"maria-ana-baptista",fullName:"Maria Ana Baptista"},{id:"16695",title:"Dr.",name:"Rachid",middleName:null,surname:"Omira",slug:"rachid-omira",fullName:"Rachid Omira"},{id:"92702",title:"Prof.",name:"Frederic",middleName:null,surname:"Leone",slug:"frederic-leone",fullName:"Frederic Leone"},{id:"148352",title:"MSc.",name:"Samira",middleName:null,surname:"Mellas",slug:"samira-mellas",fullName:"Samira Mellas"},{id:"148353",title:"Prof.",name:"Bendahou",middleName:null,surname:"Zourarah",slug:"bendahou-zourarah",fullName:"Bendahou Zourarah"},{id:"148356",title:"Prof.",name:"Jean-Philippe",middleName:null,surname:"Cherel",slug:"jean-philippe-cherel",fullName:"Jean-Philippe Cherel"},{id:"157593",title:"Prof.",name:"Nancy",middleName:null,surname:"Meschinet De Richemond",slug:"nancy-meschinet-de-richemond",fullName:"Nancy Meschinet De Richemond"}]},{id:"63921",title:"Eight Types of BG Models and Discretization",slug:"eight-types-of-bg-models-and-discretization",totalDownloads:933,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Eight types of the BG models are introduced in this chapter. The Type 1 is a model using wave parameters at the breaking point. In the Type 2, the effect of longshore sand transport due to the effect of the longshore gradient of breaker height is included with an additional term given by Ozasa and Brampton. In the Type 3, the intensity of sand transport P is assumed to be proportional to the third power of the amplitude of the bottom oscillatory velocity um due to waves, and in the Type 4, P is given by the wave energy dissipation rate due to wave breaking at a local point. In the Type 5, wave power is calculated using the coordinate system different from that for the calculation of beach changes to predict the topographic changes of an island or a cuspate foreland in a shallow water body under the action of waves randomly incident from every direction. In the Type 6, the height of wind waves is predicted using Wilson’s formula using the wind fetch distance and wind velocity, and then sand transport fluxes are calculated. The Type 7 is a model for predicting the formation of the ebb-tidal delta under the combined effect of waves and ebb-tidal currents with an analogy of the velocity distribution of ebb-tidal currents to the wave diffraction coefficient, which can be calculated by the angular spreading method for irregular waves. In the Type 8, the effect of the nearshore currents induced by forced wave breaking is incorporated into the model by calculating the nearshore currents, taking both the wave field and the current velocity at a local point into account.",book:{id:"6012",slug:"morphodynamic-model-for-predicting-beach-changes-based-on-bagnold-s-concept-and-its-applications",title:"Morphodynamic Model for Predicting Beach Changes Based on Bagnold's Concept and Its Applications",fullTitle:"Morphodynamic Model for Predicting Beach Changes Based on Bagnold's Concept and Its Applications"},signatures:"Takaaki Uda, Masumi Serizawa and Shiho Miyahara",authors:[{id:"13491",title:"Dr.",name:"Takaaki",middleName:null,surname:"Uda",slug:"takaaki-uda",fullName:"Takaaki Uda"}]},{id:"57606",title:"Analysis of Dynamic Effects on the Brazilian Vertical Datum",slug:"analysis-of-dynamic-effects-on-the-brazilian-vertical-datum",totalDownloads:952,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"This chapter presents a methodology of analyzing the dynamic effect from mean sea level variations, based on Global Navigation Satellite System (GNSS) data, velocity models, tide gauge observations, and satellite altimetry data. GNSS observations were processed in order to obtain the variation of up coordinate required to identify the possible crust movements. Velocity model served as a comparative basis to verify the obtained results from the GNSS data processing and served as a basis for analyzing the time periods without GNSS information. Tide gauge data were used to evaluate the sea level temporal evolution in the Imbituba Brazilian Vertical Datum (I-BVD). Satellite altimetry data were used for checking the results from the GNSS and the tide gauge time series. The analyses were based on time series of observations by GNSS from 2007 until 2016, tide gauge from 1948 until 1968 and 2001 until 2016, and satellite altimetry data from 1991 until 2015 from different missions. As basis for the analysis, it used GNSS SIRGAS-CON stations, the SIRGAS velocity model (VEMOS), and NUVEL velocity model. Considering the discrimination of the crust vertical movement (GNSS processing) from the results obtained with the tide gauge observations, it was observed that there is an evidence of mean sea level (MSL) rising approximately +2.24 ± 0.4 mm/year.",book:{id:"6195",slug:"sea-level-rise-and-coastal-infrastructure",title:"Sea Level Rise and Coastal Infrastructure",fullTitle:"Sea Level Rise and Coastal Infrastructure"},signatures:"Luciana M. Da Silva, Sílvio R.C. De Freitas and Regiane Dalazoana",authors:[{id:"208387",title:"Dr.",name:"Luciana",middleName:"Maria",surname:"Da Silva",slug:"luciana-da-silva",fullName:"Luciana Da Silva"},{id:"209224",title:"Dr.",name:"Sílvio",middleName:null,surname:"De Freitas",slug:"silvio-de-freitas",fullName:"Sílvio De Freitas"},{id:"209225",title:"Dr.",name:"Regiane",middleName:null,surname:"Dalazoana",slug:"regiane-dalazoana",fullName:"Regiane Dalazoana"}]},{id:"58909",title:"Coastal Disasters and Remote Sensing Monitoring Methods",slug:"coastal-disasters-and-remote-sensing-monitoring-methods",totalDownloads:1113,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Coastal disaster is abnormal changes caused by climate change, human activities, geological movement or natural environment changes. According to formation cause, marine disasters as storm surges, waves, Tsunami coastal erosion, sea-level rise, red tide, seawater intrusion, marine oil spill and soil salinization. Remote sensing technology has real-time and large-area advantages in promoting the monitoring and forecast ability of coastal disaster. Relative to natural disasters, ones caused by human factors are more likely to be monitored and prevented. In this paper, we use several remote sensing methods to monitor or forecast three kinds of coastal disaster cause by human factors including red tide, sea-level rise and oil spilling, and make proposals for infrastructure based on the research results. The chosen method of monitoring red tide by inversing chlorophyll-a concentration is improved OC3M Model, which is more suitable for the coastal zone and higher spatial resolution than the MODIS chlorophyll-a production. We monitor the sea-level rise in coastal zone through coastline changes without artificial modifications. The improved Lagrangian model can simulate the trajectory of oil slick efficiently. Making the infrastructure planning according the coastal disasters and features of coastline contributes to prevent coastal disaster and coastal ecosystem protection. Multi-source remote sensing data can effectively monitor and prevent coastal disaster, and provide planning advices for coastal infrastructure construction.",book:{id:"6195",slug:"sea-level-rise-and-coastal-infrastructure",title:"Sea Level Rise and Coastal Infrastructure",fullTitle:"Sea Level Rise and Coastal Infrastructure"},signatures:"Yan Yu, Shengbo Chen, Tianqi Lu and Siyu Tian",authors:[{id:"162887",title:"Prof.",name:"Shengbo",middleName:null,surname:"Chen",slug:"shengbo-chen",fullName:"Shengbo Chen"},{id:"220026",title:"Dr.",name:"Yan",middleName:null,surname:"Yu",slug:"yan-yu",fullName:"Yan Yu"}]}],onlineFirstChaptersFilter:{topicId:"839",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:99,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:289,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,annualVolume:11406,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. 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\r\n\tThe Business and Management series topic focuses on the most pressing issues confronting organizations today and in the future. Businesses are trying to figure out how to lead in a time of global uncertainty. In emerging markets, issues such as ill-defined or unstable policies, as well as corrupt practices, can be hugely problematic. Changes in governments can result in new policy, regulations, and interest rates, all of which can be detrimental to foreign businesses and investments. A growing trend towards economic nationalism also makes the current global political landscape potentially hostile towards international businesses.
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\r\n\tThe demographic shifts are creating interesting challenges. People are living longer, resulting to an aging demographic. We have a large population of older workers and retirees who are living longer lives, combined with a declining birthrate in most parts of the world. Businesses of all types are looking at how technology is affecting their operations. Several questions arise, such as: How is technology changing what we do? How is it transforming us internally, how is it influencing our clients and our business strategy? It is about leveraging technology to improve efficiency, connect with customers more effectively, and drive innovation. The majority of innovative companies are technology-driven businesses. Realizing digital transformation is today’s top issue and will remain so for the next five years. Improving organizational agility, expanding portfolios of products and services, creating, and maintaining a culture of innovation, and developing next -generation leaders were also identified as top challenges in terms of both current and future issues.
\r\n
\r\n\tThe most sustained profitable growth occurs when a company expands its core business into an adjacent space. This has significant implications for management because innovation in business ecosystems differs from traditional, vertically integrated firms. Every organization in the ecosystem must be aware of the bigger picture. Innovation in ecosystems necessitates collaborative action to invent and appraise, efficient, cross-organizational knowledge flows, modular architectures, and good stewardship of legacy systems. It is built on multiple, interconnected platforms. Environmental factors have already had a significant impact in the West and will continue to have an impact globally. Businesses must take into account the environmental impact of their daily operations. The advantage of this market is that it is expected to grow more rapidly than the overall economy. Another significant challenge is preparing the next generation of leaders to elevate this to the number one priority within the next five years. There can be no culture of innovation unless there is diverse leadership or development of the next generation of leaders; and these diverse, next-generation leaders are the ones who will truly understand the digital strategies that will drive digital transformation.
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