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Thornton",slug:"james-f.-thornton"},{id:"60354",title:"Ms",name:"Emily",middleName:"Diane",surname:"Rapstine",fullName:"Emily Rapstine",slug:"emily-rapstine"}]},{id:"18929",title:"Penis-Sparing Surgery with Neo-Glans Reconstruction for Benign, Premalignant or Malignant Penile Lesions",slug:"penis-sparing-surgery-with-neo-glans-reconstruction-for-benign-premalignant-or-malignant-penile-lesi",signatures:"Enzo Palminteri, Fernando Fusco, Elisa Berdondini and Andrea Salonia",authors:[{id:"63021",title:"Dr.",name:"Enzo",middleName:null,surname:"Palminteri",fullName:"Enzo Palminteri",slug:"enzo-palminteri"},{id:"63022",title:"Prof.",name:"Ferdinando",middleName:null,surname:"Fusco",fullName:"Ferdinando Fusco",slug:"ferdinando-fusco"},{id:"63023",title:"Prof.",name:"Elisa",middleName:null,surname:"Berdondini",fullName:"Elisa Berdondini",slug:"elisa-berdondini"},{id:"63024",title:"Prof.",name:"Andrea",middleName:null,surname:"Salonia",fullName:"Andrea Salonia",slug:"andrea-salonia"}]},{id:"18930",title:"Skin and Soft Tissue Injuries in Congenital Vascular Malformations",slug:"skin-and-soft-tissue-injuries-in-congenital-vascular-malformations",signatures:"Kyung-Bok Lee and Dong-Ik Kim",authors:[{id:"51380",title:"Prof.",name:"Dong-Ik",middleName:null,surname:"Kim",fullName:"Dong-Ik Kim",slug:"dong-ik-kim"},{id:"59461",title:"Dr.",name:"Kyung-Bok",middleName:null,surname:"Lee",fullName:"Kyung-Bok Lee",slug:"kyung-bok-lee"}]},{id:"18931",title:"Oral Mucosa Graft",slug:"oral-mucosa-graft",signatures:"Ismaila A Mungadi and Ngwobia P Agwu",authors:[{id:"45350",title:"Prof.",name:"Ismaila",middleName:"Arzika",surname:"Mungadi",fullName:"Ismaila Mungadi",slug:"ismaila-mungadi"},{id:"59344",title:"Dr.",name:"Peter",middleName:"Ngwobia",surname:"Agwu",fullName:"Peter Agwu",slug:"peter-agwu"}]},{id:"18932",title:"Full-Thickness Skin Grafts in Reconstructive Dermatologic Surgery of Nasal Defects",slug:"full-thickness-skin-grafts-in-reconstructive-dermatologic-surgery-of-nasal-defects",signatures:"Carmen Fernández-Antón Martínez and Ricardo Suárez-Fernández",authors:[{id:"55130",title:"Dr.",name:"Carmen",middleName:null,surname:"Fernández-Antón Martínez",fullName:"Carmen Fernández-Antón Martínez",slug:"carmen-fernandez-anton-martinez"},{id:"59334",title:"Dr.",name:"Ricardo María",middleName:null,surname:"Suárez Fernández",fullName:"Ricardo María Suárez Fernández",slug:"ricardo-maria-suarez-fernandez"}]},{id:"18933",title:"Surgical Treatment of Post-Burn Trophic Ulcers and Cicatrices of the Foot Calcaneal Area",slug:"surgical-treatment-of-post-burn-trophic-ulcers-and-cicatrices-of-the-foot-calcaneal-area",signatures:"Babur M. Shakirov",authors:[{id:"49829",title:"Prof.",name:"Babur",middleName:null,surname:"Shakirov",fullName:"Babur Shakirov",slug:"babur-shakirov"}]},{id:"18934",title:"Preputial Skin Grafts",slug:"preputial-skin-grafts",signatures:"Ahmet Bulent Dogrul and Kaya Yorganci",authors:[{id:"51997",title:"Prof.",name:"Kaya",middleName:null,surname:"Yorganci",fullName:"Kaya Yorganci",slug:"kaya-yorganci"},{id:"59910",title:"Dr.",name:"Ahmet Bulent",middleName:null,surname:"Dogrul",fullName:"Ahmet Bulent Dogrul",slug:"ahmet-bulent-dogrul"}]},{id:"18935",title:"Treatment of Adult-Acquired Buried Penis",slug:"treatment-of-adult-acquired-buried-penis",signatures:"W. Britt Zimmerman and Richard A. Santucci",authors:[{id:"52597",title:"Dr.",name:"W. Britt",middleName:null,surname:"Zimmerman",fullName:"W. Britt Zimmerman",slug:"w.-britt-zimmerman"},{id:"59671",title:"Dr.",name:"Richard A.",middleName:null,surname:"Santucci",fullName:"Richard A. Santucci",slug:"richard-a.-santucci"}]},{id:"18936",title:"Skin Graft Preservation",slug:"skin-graft-preservation",signatures:"Liangpeng Ge, Zhenggen Huang and Hong Wei",authors:[{id:"50490",title:"Dr.",name:"Hong",middleName:null,surname:"Wei",fullName:"Hong Wei",slug:"hong-wei"},{id:"57718",title:"Dr.",name:"Zhenggen",middleName:null,surname:"Huang",fullName:"Zhenggen Huang",slug:"zhenggen-huang"}]},{id:"18937",title:"Comparative Study of Skin Graft Tolerance and Rejection in the Frog Xenopus Laevis",slug:"comparative-study-of-skin-graft-tolerance-and-rejection-in-the-frog-xenopus-laevis",signatures:"Hristina Nedelkovska and Jacques Robert",authors:[{id:"45072",title:"Dr.",name:"Jacques",middleName:null,surname:"Robert",fullName:"Jacques Robert",slug:"jacques-robert"},{id:"59684",title:"Ms",name:"Hristina",middleName:null,surname:"Nedelkovska",fullName:"Hristina Nedelkovska",slug:"hristina-nedelkovska"}]},{id:"18938",title:"The Effect of Human Recombinant Erythropoietin (rHuEPO) and Tacrolimus (FK506) in Autologous and Homologous Full Thickness Skin Graft (FTSG) Take and Viability in a Rat Model",slug:"the-effect-of-human-recombinant-erythropoietin-rhuepo-and-tacrolimus-fk506-in-autologous-and-homolog",signatures:"Dimitrios Karypidis, Despina Perrea, Othon Papadopoulos and Alkiviadis Kostakis",authors:[{id:"45544",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Karypidis",fullName:"Dimitrios Karypidis",slug:"dimitrios-karypidis"},{id:"59271",title:"Dr.",name:"Despina",middleName:null,surname:"Perrea",fullName:"Despina Perrea",slug:"despina-perrea"},{id:"59272",title:"Prof.",name:"Othon",middleName:null,surname:"Papadopoulos",fullName:"Othon Papadopoulos",slug:"othon-papadopoulos"}]},{id:"18939",title:"Recent Innovation in Pretreatment for Skin Grafts Using Regenerative Medicine in the East",slug:"recent-innovation-in-pretreatment-for-skin-grafts-using-regenerative-medicine-in-the-east",signatures:"Hitomi Sano and Shigeru Ichioka",authors:[{id:"52821",title:"Prof.",name:"Shigeru",middleName:null,surname:"Ichioka",fullName:"Shigeru Ichioka",slug:"shigeru-ichioka"},{id:"59380",title:"Dr.",name:"Hitomi",middleName:null,surname:"Sano",fullName:"Hitomi Sano",slug:"hitomi-sano"}]},{id:"18940",title:"Application of the Nanocrystalline Silver in Treatment of Burn Wounds in Children",slug:"application-of-the-nanocrystalline-silver-in-treatment-of-burn-wounds-in-children",signatures:"Maya Argirova and Ognian Hadjiiski",authors:[{id:"58705",title:"PhD.",name:"Maya",middleName:null,surname:"Argirova",fullName:"Maya Argirova",slug:"maya-argirova"},{id:"62439",title:"Prof.",name:"Ognian",middleName:null,surname:"Hadjiiski",fullName:"Ognian Hadjiiski",slug:"ognian-hadjiiski"}]},{id:"18941",title:"How Does Human Amniotic Membrane Help Major Burn Patients Who Need Skin Grafting: New Experiences",slug:"how-does-human-amniotic-membrane-help-major-burn-patients-who-need-skin-grafting-new-experiences",signatures:"Ali Akbar Mohammadi and Mohammad Kazem Mohammadi",authors:[{id:"50621",title:"Prof.",name:"Ali Akbar",middleName:null,surname:"Mohammadi",fullName:"Ali Akbar Mohammadi",slug:"ali-akbar-mohammadi"},{id:"58843",title:"Dr.",name:"Mohammad Kazem",middleName:null,surname:"Mohammadi",fullName:"Mohammad Kazem Mohammadi",slug:"mohammad-kazem-mohammadi"}]},{id:"18942",title:"Influence of Microorganisms on the Healing of Skin Grafts from Chronic Venous Leg Wounds",slug:"influence-of-microorganisms-on-the-healing-of-skin-grafts-from-chronic-venous-leg-wounds",signatures:"Tine Yding Wolff, Thomas Bjarnsholt, Klaus Kirketerp-Møller and Trine Rolighed Thomsen",authors:[{id:"49457",title:"Dr.",name:"Trine Rolighed",middleName:null,surname:"Thomsen",fullName:"Trine Rolighed Thomsen",slug:"trine-rolighed-thomsen"},{id:"49462",title:"Dr.",name:"Thomas",middleName:null,surname:"Bjarnsholt",fullName:"Thomas Bjarnsholt",slug:"thomas-bjarnsholt"},{id:"49463",title:"Dr.",name:"Klaus",middleName:null,surname:"Kirketerp-Møller",fullName:"Klaus Kirketerp-Møller",slug:"klaus-kirketerp-moller"},{id:"60054",title:"MSc",name:"Tine",middleName:"Yding",surname:"Wolff",fullName:"Tine Wolff",slug:"tine-wolff"}]},{id:"18943",title:"Clinical Evaluation of Glyaderm, a Dermal Substitute Based on Glycerinized Donor Skin",slug:"clinical-evaluation-of-glyaderm-a-dermal-substitute-based-on-glycerinized-donor-skin",signatures:"Pirayesh A., Richters CD, Hoeksema H, Verbelen J, Heyneman A and Monstrey S.",authors:[{id:"56158",title:"Dr.",name:"Cornelia",middleName:null,surname:"Richters",fullName:"Cornelia Richters",slug:"cornelia-richters"}]},{id:"18944",title:"External Wire Frame Fixation for Skin Grafts",slug:"external-wire-frame-fixation-for-skin-grafts",signatures:"Rei Ogawa and Hiko Hyakusoku",authors:[{id:"45225",title:"Dr.",name:"Rei",middleName:null,surname:"Ogawa",fullName:"Rei Ogawa",slug:"rei-ogawa"},{id:"59886",title:"Prof.",name:"Hiko",middleName:null,surname:"Hyakusoku",fullName:"Hiko Hyakusoku",slug:"hiko-hyakusoku"}]},{id:"18945",title:"Efficacy of Autogenous Dermis Graft for Wound Coverage",slug:"efficacy-of-autogenous-dermis-graft-for-wound-coverage",signatures:"Seung-Kyu Han",authors:[{id:"60148",title:"Prof.",name:"Seung-Kyu",middleName:null,surname:"Han",fullName:"Seung-Kyu Han",slug:"seung-kyu-han"}]},{id:"18946",title:"Cryopreservation of Skin Tissues for Skin Grafts",slug:"cryopreservation-of-skin-tissues-for-skin-grafts",signatures:"Suong-Hyu Hyon",authors:[{id:"51336",title:"Prof.",name:"Suong-Hyu",middleName:null,surname:"Hyon",fullName:"Suong-Hyu Hyon",slug:"suong-hyu-hyon"}]},{id:"18947",title:"Sentinel Skin Allograft for Monitoring of Composite Tissue Transplants Rejection",slug:"sentinel-skin-allograft-for-monitoring-of-composite-tissue-transplants-rejection",signatures:"Zamfirescu DG, Lascar I and Lanzetta M",authors:[{id:"52765",title:"Dr.",name:"Dragos",middleName:null,surname:"Zamfirescu",fullName:"Dragos Zamfirescu",slug:"dragos-zamfirescu"}]},{id:"18948",title:"Immunological Considerations for Inducing Skin Graft Tolerance",slug:"immunological-considerations-for-inducing-skin-graft-tolerance",signatures:"Ethel J. Gordon",authors:[{id:"56692",title:"Dr.",name:"Ethel",middleName:null,surname:"Gordon",fullName:"Ethel Gordon",slug:"ethel-gordon"}]}]}],publishedBooks:[{type:"book",id:"368",title:"Skin Grafts",subtitle:"Indications, Applications and Current Research",isOpenForSubmission:!1,hash:"78bb532197274bb1fe80d42c800a1b00",slug:"skin-grafts-indications-applications-and-current-research",bookSignature:"Marcia Spear",coverURL:"https://cdn.intechopen.com/books/images_new/368.jpg",editedByType:"Edited by",editors:[{id:"61993",title:"Dr.",name:"Marcia",surname:"Spear",slug:"marcia-spear",fullName:"Marcia Spear"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"740",title:"Neck Dissection",subtitle:"Clinical Application and Recent Advances",isOpenForSubmission:!1,hash:"198a38d9effbbc4b524e15b024033bac",slug:"neck-dissection-clinical-application-and-recent-advances",bookSignature:"Raja Kummoona",coverURL:"https://cdn.intechopen.com/books/images_new/740.jpg",editedByType:"Edited by",editors:[{id:"93854",title:"Prof.",name:"Raja",surname:"Kummoona",slug:"raja-kummoona",fullName:"Raja Kummoona"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1760",title:"The Role of Osteotomy in the Correction of Congenital and Acquired Disorders of the Skeleton",subtitle:null,isOpenForSubmission:!1,hash:"9661cdebd682842816ac472a9330e6eb",slug:"the-role-of-osteotomy-in-the-correction-of-congenital-and-acquired-disorders-of-the-skeleton",bookSignature:"James P. Waddell",coverURL:"https://cdn.intechopen.com/books/images_new/1760.jpg",editedByType:"Edited by",editors:[{id:"112781",title:"Prof.",name:"James",surname:"Waddell",slug:"james-waddell",fullName:"James Waddell"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6211",title:"Medical and Surgical Education",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"6c32a9763401f2d6e07b50f3e6451870",slug:"medical-and-surgical-education-past-present-and-future",bookSignature:"Georgios Tsoulfas",coverURL:"https://cdn.intechopen.com/books/images_new/6211.jpg",editedByType:"Edited by",editors:[{id:"57412",title:"Prof.",name:"Georgios",surname:"Tsoulfas",slug:"georgios-tsoulfas",fullName:"Georgios Tsoulfas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6705",title:"Organ Donation and Transplantation",subtitle:"Current Status and Future Challenges",isOpenForSubmission:!1,hash:"e1ab81caf9179b0618c80dcd9bfd84a3",slug:"organ-donation-and-transplantation-current-status-and-future-challenges",bookSignature:"Georgios Tsoulfas",coverURL:"https://cdn.intechopen.com/books/images_new/6705.jpg",editedByType:"Edited by",editors:[{id:"57412",title:"Prof.",name:"Georgios",surname:"Tsoulfas",slug:"georgios-tsoulfas",fullName:"Georgios Tsoulfas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"1760",title:"The Role of Osteotomy in the Correction of Congenital and Acquired Disorders of the Skeleton",subtitle:null,isOpenForSubmission:!1,hash:"9661cdebd682842816ac472a9330e6eb",slug:"the-role-of-osteotomy-in-the-correction-of-congenital-and-acquired-disorders-of-the-skeleton",bookSignature:"James P. Waddell",coverURL:"https://cdn.intechopen.com/books/images_new/1760.jpg",editedByType:"Edited by",editors:[{id:"112781",title:"Prof.",name:"James",surname:"Waddell",slug:"james-waddell",fullName:"James Waddell"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"79568",title:"Folliculogenesis, Fertility and Biotechnology in Dairy Cattle",doi:"10.5772/intechopen.101243",slug:"folliculogenesis-fertility-and-biotechnology-in-dairy-cattle",body:'Dairy farming plays an essential role in the global socioeconomic scenario, being one of the most traditional rural activities and fundamental for agribusiness. Milk is one of the most complete and most consumed food globally, in addition to providing a social function, generating thousands of direct and indirect jobs throughout the production chain. The development of new technologies should add more efficiency to the milk production chain, a constant challenge for several sectors involved in the segment.
The use of animal reproduction biotechnologies has contributed to the increase in animal productivity and has been one of the main responsible for the increase in milk production. The current scenario is the search for a model capable of providing high production efficiency concerning animal welfare without harming the environment and with the most advanced reproductive techniques for obtaining pregnancies and genetic improvement. In this way, ovarian physiology is a key aspect to contribute to the efficiency of dairy production.
The ovarian follicular population is characterized by the total amount of follicles present in the ovary. Each follicle contains an oocyte, so it is known that there are a great number of oocytes in the ovary. However, only a small portion of the ovarian follicles undergo ovulation. Therefore, the ovarian follicular reserve is an important indicator of fertility in cattle, which may influence the applicability of reproductive biotechniques.
This chapter addresses the mechanism of folliculogenesis and the most recent research. It also brings discussions on how reproductive biotechniques can influence fertility in dairy cattle.
The origin of the female reproductive system is still in embryonic life in the sublumbar region located caudally to the kidneys. The primordial germ cells, which will give rise to the germline formation, originate in the proximal epiblast and then move from the yolk sac to the gonadal ridges through the mesentery, around day 30 of germinal development [1]. At this moment, the Müller and Wolff ducts are still present, which will give rise to the female and male reproductive tract, respectively.
After the colonization of the ridges, around 35 days of gestation, the differentiation process begins by specifying the somatic cells of the ridge, where Sertoli cells will originate from the XY chromosome, and the granulosa cells will originate from the XX chromosome. There is an involution of Wolff’s duct (or mesonephros) and development of Müller’s duct (or paramesonephric) in the escarpments. In males, as they inherit the testicles determining factor (TDF) from the Y chromosome, Sertoli cells release the anti-müllerian hormone (AMH) and inhibit the development of Müller’s ducts [2, 3]. After this process, they are formed as oogonia that through mitotic and meiotic divisions form a nest of oogonia in a tubular shape, and then a process of differentiation into oocytes begins [4].
Gonadal structures called germline cysts are elevated in the ovigerous cords and surrounded by a basement membrane shortly after colonization of the gonadal ridges by primordial germ cells. Meiotic divisions are initiated until the process is stopped in meiosis prophase I when primary oocytes are already formed. The primary oocytes are surrounded by a layer of undifferentiated pregranulosa cells [5]. The interruption of meiosis can last for years until a given follicle enters the growth process, resuming meiosis and continuing the follicular development through the primordial follicle until its final stage in the antral follicle [6].
It is known that folliculogenesis depends on interactions between the somatic cells of the follicle and the oocyte, so the communication between the granulosa and theca cells with the oocyte is essential for follicular development and growth to occur [7, 8]. The passage from the primordial follicle to the primary follicle is a transition phase and is characterized by the action of specific growth factors for each stage of folliculogenesis [9]. In bovine species, the so-called follicular growth waves correspond to a stimulus for the recruitment of preantral follicles.
Once the primordial follicle is recruited, whose granulosa cells are flat, it becomes the primary follicle and there is a transition between the flat cells to the cuboidal-shaped granulosa cells [9]. At this stage, the zona pellucida appears, which will remain around the oocyte throughout the follicle’s development. Continuing to grow, the secondary follicle is constituted when the granulosa cells multiply and form two layers of cubic morphology, in addition to the emergence of the first theca cells [10].
The growth of these secondary follicles (when they reach approximately 4 mm in diameter) is regulated by the follicle-stimulating hormone (FSH), which has its receptors in the granulosa cells. When they reach a larger size (approximately 7–9 mm in diameter), they start to be controlled by luteinizing hormone (LH). At this stage, the follicle is already characterized as tertiary and has LH receptors in the theca cells that are already entirely organized, and the formation of the follicular antrum can be observed [11, 12]. The phases of follicular development are shown in Figure 1.
Schematic sequence of complete follicular development.
The follicular population may vary between individuals, and some factors such as genetics, breed, age, species, and hormone levels can influence the number of follicles present in the ovaries [13]. For bovine females, it is estimated that the number of follicles at birth is about 235,000 [14].
An increase in the number of antral follicles present in the ovary and stimulated by gonadotrophin secretion is influenced by body development in heifers [15]. Endocrine activity at first seems to be controlled by suppressing negative feedback mechanisms until the heifer has a good body condition to initiate the estrous cycle and reproduction activities [16, 17, 18].
The first ovulation in heifers is marked by a gradual increase in LH secretion, which leads to the development of the antral follicles and the secretion of estrogen. At birth, antral follicles are not typically present in the ovaries, and the number of follicles increases when heifers reach 2 months of age. After that, the number of follicles declines at 5 months of age, and some changes continue to occur throughout the productive life of the female [19, 20, 21].
Ovarian follicular population is highly variable among species, a concept that is well established [20, 21, 22] and has been already reported in cattle [23]. In recent years, numerous studies have focused on the ovarian follicular population and its influence on reproductive activities, as well as on animal reproduction biotechniques [22, 24]. The antral follicle count (AFC) is a strategy to identify different profiles of cows, performing transrectal B-mode ultrasonography and counting all follicles larger than 3 mm [25]. The total number of follicles counted in the pair of ovaries is added up, and the cow is classified as low, medium, or high AFC. A feature in cattle is the high variability of AFC between animals, but it is known that there is high repeatability in the same individual [19, 26, 27]. The appearance of the ovary on ultrasound examination of cows with high and low AFC is presented in Figure 2.
Aspect of the ovary on ultrasound examination of cows with different counts of antral follicles (AFC). On the right (A) cow with low AFC, and the left (B) cow with high AFC. Images were generated via the transrectal route with the equipment model S8v (SonoScape®) with a frequency of 8.6 MHz and a linear transducer of 5–10.0 MHz.
Furthermore, according to [28], it has already been established that the concentrations of anti-müllerian hormone (AMH), which is released by the granulosa cells of growing ovarian follicles, are positively related to the entry into puberty of bovine females. In other words, the higher serum concentrations of this hormone are, the higher AFC will be [27]. AMH is a glycoprotein that belongs to the TGF-β growth factor family [29] and it is correlated with follicular growth [30]. AMH is in the granulosa cells and it is responsible for the growth of preantral and antral follicles [31] and follicular growth modulator through the control of ovarian follicular reserve depletion [32].
The intrafollicular AMH expression increases until the follicle reaches 5 mm in cows and then decreases as the follicle reaches the antral stage and increases in size [31]. The positive correlation of AMH with the ovarian follicular population has already been described in previous studies [33, 34]. Thus, the measurement of AMH can be a method of predicting AFC [35]. In
Reproductive biotechniques, such as embryo transfer (ET) and IVEP, depends on the population of antral follicles present in the ovary of donor females to succeed. Among other factors that interfere with ET and IVEP, it is important to mention genetics, breed, and age [37, 38]. High AFC bovine females have been described to have a greater number of viable embryos produced
In contrast, a high conception rate was observed after the use of TAI in low AFC females
Donors with a high number of antral follicles have been selected, mainly for OPU-
In summary, several studies have tried to verify the influence and the correlation of AFC in the reproductive performance of bovine females. So far, it is not possible to establish the role of AFC in fertility parameters due to the controversial results. Although it is quite predictable that AFC may be related to reproductive efficiency, a better understanding of the subject is necessary. Furthermore, considering basic research, it is necessary to elucidate some aspects of follicular physiology that remain unknown [47].
Increasing the productive efficiency of a herd is one of the great challenges for dairy cattle farming. In the past, genetic selection programs sought essential characteristics for increasing milk production, with effective gains in milk quantity and quality, but reproductive efficiency was disregarded. In recent years, several works have been presented to increase milk production and increase reproductive performance, a key association for efficient dairy farming.
Considering the importance of a sustainable, intensive, and economically viable production system, achieving the reproductive efficiency of the dairy herd is crucial for the effects on profitability by the number of offspring produced, genetic progress, and the shorter interval between lactations. This is a great challenge, as there is low heritability between production and reproduction traits. Therefore, the crucial importance of precisive reproductive assistance is highlighted, providing maximum production efficiency in the smallest possible area and respecting the aspects of animal comfort.
Despite the rapid development of the technique since its emergence in the late 1980s, until recently, IVEP was used only as a last resource when traditional techniques failed. However, the high genetic gains provided to the herds, obtaining a greater number of pregnancies concerning
Holstein cows typically have lower oocyte production when subjected to IVEP. However, it is possible to obtain good results by performing a pre-selection of females with a high number of antral follicles using ultrasound. It is important to highlight that non-lactating females often have a higher number of follicles and oocytes.
Until a few years ago, some obstacles prevented the large-scale use of IVEP in dairy cattle. One of them was the large number of calves born from unwanted sex (male), which significantly increased the production cost. Another difficulty was the distance, often thousands of kilometers, between the laboratories and the properties where the recipient cows were located. The inefficiency of cryopreservation techniques for IVP embryos, especially when dealing with
These two major obstacles have now been overcome, making large-scale
In addition, some alternatives can be employed to improve the methods that assist in the recovery of better-quality oocytes and a higher competence in OPU to obtain more interesting results in embryo production. In this context, the follicular wave synchronization before OPU and consider the influence of the antral follicle population seem to be good alternatives [50].
Dairy European breeds, such as Holstein and Jersey, suffer great discomfort under high temperatures and high humidity conditions. Therefore, failures in cyclicity and the demonstration of estrus occur, making management difficult and compromising AI results. Furthermore, it is known that embryos are naturally more resistant to heat stress than gametes, which can suffer degeneration and further reduce pregnancy rates in the summer [51]. The transfer of embryos 7 days after fertilization avoids the harmful effects before this period, providing more advantageous rates than AI [52, 53, 54]. For dairy cattle, therefore, the use of transferred embryos seems to be the most viable option, especially in periods of excessive heat [55].
In AI, the number of descendants of genetically selected bulls is multiplied. IVEP, in turn, also generates descendants of females of high genetic merit, causing an even more significant impact on the improvement of a herd. Greater genetic gain is achieved in each generation with the transfer of embryos produced
In some dairy farms, cows with better genetic potential are used as embryo donors and recipients. Thus, an efficient genetic selection from animals in the herd becomes possible. As for the economic aspect, with the number of pregnancies in IVEP, it is possible to produce embryos at affordable costs, making the embryo commercially attractive compared to semen [56]. Another advantage is the better use of high-value semen due to the possibility of fertilizing ten or more cows with a single dose.
The use of conventional semen, both in AI and
The most used technique for semen sexing is flow cytometry, which offers an accuracy of 85–95% [59]. However, during the sexing process, the sperm may be damaged, which might compromise their viability, reducing the fertilization potential and embryonic development [60]. The sexing process reduces sperm motility, compromising AI indices. [61] Related that the mean conception rate after AI between 2012 and 2016 was 56.9% with conventional semen and 47.3% using sexed semen. In IVEP, however, the method allows obtaining very satisfactory rates of blastocysts, with quality similar to those produced with conventional semen, since this technique requires fewer viable spermatozoa [62, 63]. Generally, the conception rate obtained with sexed semen is 50–60% of the rates obtained with conventional semen in cows and 70–90% of conventional semen in heifers [64].
As there is a reduction in fertility using this semen, some strategies are currently suggested to improve conception rates in insemination programs that use sexed semen. First, it is recommended to use this semen in heifers and most in the first three services due to greater fertility. In AI programs with heat observation, the highest conception rates were achieved, with AI being performed between 16 and 24 h after the onset of heat [65]. Finally, in TAI programs, the best rates were achieved with semen deposition 60 h after removing the progesterone source [66].
In the
The
The production of embryos by SOV also does not allow pregnant cows, while in IVEP, this is possible. Follicular aspiration can be performed as long as the ovaries can be manipulated without being subjected to excessive traction. The process flow of
Schematic sequence of steps in the
Schematic sequence of steps in the
The cryopreservation of bovine embryos generated
The greater sensitivity of these embryos to low temperatures is mainly due to the greater accumulation of lipids in the cytoplasm [71]. Lipids, made up mostly of triacylglycerols, directly affect the survival of embryos during cooling, as they can undergo irreversible changes and severely compromise development. An alternative method to promote chemical delipidation of embryos and increase cryotolerance by decreasing lipid accumulation has been related [72]. Forskolin, for example, a compost derived from the Indian plant
Among the cryopreservation methods, vitrification is the most used technique worldwide due to the speed of the process and its low cost [74]. On the other hand, direct transfer (DT), a technique used to simplify the
The
Due to the metabolic and morphological differences compared to those produced
Thus, if the proposal is to associate embryo transfer and sexed semen, the best strategy at the moment is the
In order to minimize the effects of early embryonic loss, the Doppler ultrasound technique has been included in reproductive programs. This non-invasive and real-time biotechnology allows the characterization of blood perfusion of reproductive organs and tissues throughout the estrous cycle and pregnancy in cattle. One of its purposes is to accurately estimate the corpus luteum (CL) functionality for the selection of recipients and for the early diagnosis of pregnancy in TAI and TETF (Fixed Time Embryo Transfer) programs.
In addition to allowing for greater accuracy in the evaluation of the recipient, another feature of the Doppler is the diagnosis of pregnancy at 20–22 days, which is early compared to the conventional system performed at 30 days after insemination. Super-early resynchronization programs developed in heifers and cows are being introduced in dairy herds, as the reduction in the interval between two TAIs promotes gains in reproductive efficiency. Despite the correct evaluation being dependent on the experience and knowledge of the operator and the correct configuration of the equipment, the popularization of the technique is consolidated every day and presents good prospects for the future.
The current scenario of reproduction biotechnology demonstrates great potential for a sustainable increase in milk production, mainly due to the increase in reproductive and productive efficiency. Furthermore, the growth in the use of reproductive biotechniques is associated with the parallel development of a support network such as veterinarians, the pharmaceutical industry, disposable materials, equipment, and service providers. The generation of employment and the need to train human resources to meet the demand for activities are intended to provide social growth.
With the possibility of obtaining an accelerated genetic gain through the shortening of the generation interval, the use of prepubertal females, mainly in the production of embryos, has aroused great commercial interest and investment in research. The genetic potential of the female must first be evaluated in advance, that is, before total production. This is feasible thanks to progress in research with genetic markers for accurate prediction of the females that will be more efficient in milk production. It is also important to consider improving equipment for OPU (oocyte recovery by Ovum pick-up). There are currently fully adapted transducers for use in very young females. Despite the good number of aspirated follicles, a challenge in this category is the low blastocyst rate, promoting limited results in IVF.
Thus, to be viable for the use of these females, the next step is to develop protocols that improve the competence of the retrieved oocyte. Gonadotropin stimulus to increase the proportion (and size) of large follicles and synchronization of follicular waves before OPU to decrease immature oocytes have been investigated. A revolution in dairy farming that has become increasingly accessible is genomic selection which has significantly altered the global dairy industry. The reduction in the generation interval from 7 to 2.5 years and the reduction of costs with progeny tests were only the first benefits presented by the gene-editing biotechnique.
Silencing, altering or replacing genes that cause problems are effective strategies to increase the productive efficiency of the herd, selecting and breeding genetically superior animals. The generation gap is likely to narrow further as assessments gain wide acceptance, as genetic gains are cumulative across generations. Genetic progress is expected as continued genetic selection is implemented. Since 2009, more than one million animals have received genetic evaluations. Although these tests are carried out primarily on male animals, genotyping costs are currently economically viable. Currently, genomic selection programs are investing more in health traits (resistance to disease), reproduction, and selection for environmentally sustainable production, including reducing waste production and gas emissions.
This change of concept, which seeks longevity and animal welfare, is because, in recent years, there has been a decline in fertility and resistance in several populations, leading to a decrease in the profitability of the herds. The increase in slaughter rates, veterinary expenses, replacement costs, and reduced milk sales were just some of the consequences of the negative impact of years of selection focusing only on milk production and animal appearance. Furthermore, the adoption of a selection index, such as evaluating the quality and viability of embryos before the transfer, increases the efficiency of the process.
An example of this has been in North America, where the implementation of a genetic-based selection program for reproductive disorders is actively researched. A high and positive genetic correlation between retained placenta and metritis is being observed, implying selection of genes to improve one trait reflecting positively on the other. This demonstrates that the increased need for genomic traits for these traits contributes to the reproductive efficiency of dairy herds.
Other characteristics that have been valued in genomic tests are identifying biomarkers considered for genetic improvement, highly correlated with reproductive performance, such as anti-müllerian hormone (AMH), and identifying relevant genes to reduce pregnancy losses. Identifying genetic markers related to the development and anticipation of the embryo and their selection to avoid embryonic losses can minimize economic damage. Another issue to be further elucidated shortly is whether genes relevant to embryonic development are positively associated with fertility traits. Estimates of the heritability of conventional reproductive traits are generally low. Even so, the progressive inclusion of genomic tests, as a routine in the field, has great potential for identifying superior animals. In the medium and long term, one perspective is that genetic improvement programs will bring consistent profitability for the dairy industry.
Genomic testing still faces challenges because a decisive outcome in the short term is unlikely. Genetic variation for economic characteristics is maintained by increased frequency of rare alleles, new mutations and changes in goals, and no selection management. Moreover, although genomic selection is being well applied at rates of genetic gain, we still know very little about the genetic structure that promotes this variation. The most relevant future challenge will probably be the incorporation of new characteristics in the selection index in breeding programs, overcoming a measurement difficulty or low heritability of them. Added to this, it is still uncertain whether traits produced over several generations emerged included in routine genomics, as gene frequencies change over time.
It is already known that the selection of some genes can directly or indirectly influence other aspects. The concern with creations called “ecologically correct” remains controversial. The inclusion of characteristics such as lower gas emissions can compromise herd productivity. It should be remembered that the increase in milk production per animal reduces the total production of residues in the atmosphere. In other words, it is something broader than simply a genetic alteration to favor an environmental issue narrowly.
Genomic testing positively changes productivity dynamics, but attention is needed to the consequences of these genetic manipulations. The pioneering application of genomic selection in cattle will lead to a series of unanticipated discoveries that could affect animals and society. An accidental finding was recently published in highly relevant research. It was discovered that two cloned bulls whose cell lineage had undergone gene editing, aiming at the characteristic of not having horns, were transgenic. The animals contained in their genome the genetic material of the bacterium used as a vector in gene editing. The Food and Drugs Administration (FDA) guarantees that intentional genomic alterations are safe for animals and anyone who consumes foods derived from them. However, there is still no universally accepted verification method for genomic editing.
Finally, with all the technological changes, the dairy herd has its premises, but the consumer market has also increased its requirements. Producers face the challenge that today there are claims for harmonic milk in ingestion (A2A2) [78], welfare for female producers, and respect for the environmental preservation area. People worldwide are looking for information about the products daily and are no longer limited to the final part of the milk production chain.
The increase in reproductive efficiency is a proposal fully adjusted to environmental sustainability. More productive herds require less area to generate more feed. Furthermore, the use of genetically improved animals according to the climatic conditions of each region prevents land competition with agriculture. As for differentiated milk production, the inclusion of bulls genotyped for the A2 allele of beta-casein accelerates aggregation of A2A2 animals in the herd.
Another critical aspect is the mandatory link between reproductive biotechnology and animal welfare. More productive animals only respond to greater reproductive efficiency if they have all vital requirements well met. Technological innovations such as robotic milking, with the cow’s autonomy about milking, signals a prospect of increased milk production with the same number of animals. A new change in concept which, adding welfare to the creation of dairy cattle will reflect positively on the profitability of producers.
All aspects of folliculogenesis remain a vast area to be studied, despite the notable progress made with previous research. It is not possible to determine the complete influence of AFC on female bovine fertility. The use of AFC as a tool to produce embryos
Overcoming the main limitations of IVEP, together with the good results and its high applicability, has contributed to the use of biotechnique on a large scale. Thus, IVEP is no longer limited to elite animals or animals that do not respond to superovulation but actively contributes to the production, improvement, and profitability of dairy production.
The transfer of IVP embryos is a great strategy to reduce the cost of high genetic value semen, and it seems to be the most viable option in periods or regions of high temperatures. Thus, IVEP has benefited dairy farms of all sizes and animals of different breeds, whether
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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. 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He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}}]}},subseries:{item:{id:"40",type:"subseries",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"