List of interlayer expansions and average crystallite size of the nanocomposites.
\r\n\t
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Currently, he is an Associate Professor at Physics Department, Kasetsart University, Thailand. He is a specialist in the development of smart sensors and intelligent systems for food, agricultural and environmental applications. He has received over twenty-eight research awards such as TRF–OHEC–SCOPUS Young Researcher Award in physical science, Invention Award from National Research Council of Thailand, Highest Citation Award for the young researcher, etc. He has served as a reviewer, guest editor, and associate editor for several scientific journals. He is Top 2% World Ranking of Scientists in Electrical & Electronic Engineering in 2020 and 2021 ranked by the Stanford University researcher team. He has published several dozens of articles in reputed journals, proceedings, book chapters, patents, and copyrights. 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Unlike other techniques such as organic syntheses where rigorous conditions are used and purification of products is mandatory, intercalation chemistry provides an excellent route to combine the properties of two materials, which often does not require product purification. Therefore, intercalation chemistry is a “green shift” for developing new materials. Vanadium pentoxide xerogel (V2O5
Intercalation of polymers into layered structures is a growing field of research with a wide range of potential applications [5]. For example, organic–inorganic nanocomposites offer promise for new engineering composites in the automotive, packaging, and aerospace industry because of their improved mechanical properties [6]. An organic–inorganic nanocomposite is a two-phase material in which the organic and inorganic phases are distributed in each other at the nanolevel. Therefore, with careful selection of the inorganic host and the guest polymer, it is possible to design materials that can be used in electrochemical energy storage devices such as in Li-ion batteries. Normally, the nanocomposite composition is controlled in order to increase its ionic conductivity at ambient temperatures so that it can be used as a solid electrolyte and/or as a cathode.
\nVanadium pentoxide xerogel is a good host material for guest molecules and ions. The intercalation of guest species into vanadium pentoxide xerogel may occur via dipole–dipole interaction, ion exchange, acid–base, coordination, and redox reactions, enabling the system to accept both neutral and charged guest species [7, 8]. Vanadium pentoxide xerogel has also shown promising redox reactions that can be utilized in Li-ion batteries. For example, Passerini et al. demonstrated that V2O5
Current conventional Li-ion batteries utilize liquid organic electrolytes [10, 11] that come with several shortcomings, which limit their widespread usage in large load applications, such as electric vehicles and stationary power. Most of these liabilities are safety-related, which include electrolyte leakage, decomposition, flammability, and a propensity to develop catastrophic short circuits. To circumvent these problems, polymer electrolytes have been extensively studied as an alternative. The search for polymer electrolytes was initiated by the discovery of ionic conduction in complexes of poly(ethylene oxide) (PEO) containing alkali metal salts [12, 13] and the suggestion that such ionic conductors could be used as electrolytes in electrochemical devices [14]. Since then many PEO derivatives have been developed with efforts to improve ionic conductivity [15, 16]. There are two main strategies used for developing PEO derivatives with increased ionic conductivity: one approach focuses on increasing ionic mobility, that is, developing polymers that are flexible and amorphous with low glass transition temperatures. The second strategy focuses on increasing ionic dissociation by placing polar subunits such as acrylamide, acrylonitrile, maleic anhydride, and carbonate along the chains to increase the polymer’s dielectric constant [17, 18]. Based on the second strategy, poly[oligo(ethylene glycol)-oxalate] (POEGO) was developed by Xu et al. [19]. They reported a maximum conductivity of 5.9 × 10−5 S cm−1 at 25°C with the complex of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), with etheric oxygen to Li-ion ratio of [EO]/[Li+] = 16. They also reported that POEGO–LiTFSI complex showed good electrochemical stability up to 4.4 V versus Li+/Li. These properties make POEGO a viable candidate for developing solid electrolytes for Li-ion batteries.
\nSeveral studies have been conducted where POEGO is intercalated into various layered structures. The intercalation is meant to improve the mechanical properties of POEGO in order to eliminate its tendency to flow under pressure, while retaining its ionic conductivity, and hence make it more suitable for use as a solid electrolyte in Li-ion batteries. For example, POEGO has been intercalated into hectorite [20], tin disulfide [21], graphite oxide [22], and molybdenum disulfide [23]. To our best knowledge, no work has been reported on the intercalation of POEGO into V2O5
The focus of this chapter is to report on the intercalation of POEGO and LiCF3SO3–POEGO complex into vanadium pentoxide xerogel and the potentials of these nanocomposites in the Li-ion battery applications. In this chapter, the lithium salt (LiCF3SO3,) and a complex of POEGO with LiCF3SO3 will be abbreviated as Li
Sodium metavanadate was purchased from Fluka. Dowex 50W-X 8, 20–50 mesh resin, and oxalic acid dihydrate were purchased from Baker. HPLC-grade methanol was purchased from Caledon. Benzene 99.9% was purchased from Aldrich. All were used as received. Poly(ethylene glycol) (PEG 400), purchased from Aldrich was dried over 3 Å molecular sieves under nitrogen purge from a Schlenk line.
\nThe synthesis of V2O5
POEGO was synthesized as reported in the literature [19]. In a typical experiment, PEG 400 (15.0 g, 0.0375 mol) was added to oxalic acid dihydrate (5.00 g, 0.0397 mol) in benzene (100 mL), and the mixture was refluxed for 4 days in a 250 mL round-bottom flask while stirring. Benzene was then removed under reduced pressure. The reaction mixture was then heated in a vacuum oven at 120°C until a clear viscous product was obtained. The use of PEG with a molecular weight of 400 means that there are, on average, nine ethyleneoxy repeating units in each oligo(ethylene glycol) oxalate group in our POEGO [19].
\nA Li-POEGO complex was prepared using the optimum ionic conductivity ratio of [EO]/Li+ = 16 as reported in the literature [19].
\nThe nanocomposites were prepared by adding POEGO dissolved in methanol to the aqueous solution of V2O5
To confirm that the polymer chains were actually intercalated into V2O5
Powder X-ray diffraction (XRD) data were collected on a Bruker AXS D8 Advance instrument equipped with a graphite monochromator, variable divergence slit, variable antiscatter slit, and a scintillation detector. Cu (K
Thermal properties of the samples were investigated using TA instruments. Thermogravimetric analysis (TGA) data were collected on a Q500 in dry air or nitrogen purge using a heating rate of 10°C/min up to 680°C. Differential scanning calorimetry (DSC) was performed on a Q100 under dry nitrogen purge using heating and cooling rates of 10°C/min and 5°C/min, respectively. The TGA and DSC data were processed using the TA Universal Analysis 2000 software. The samples were freeze-dried using a Virtis Benchtop 3.3/Vacu-Freeze dryer and left in a desiccator overnight, before analysis.
\nReflectance Fourier transform infrared (FTIR-ATR) spectra were obtained in the range 4000–400 cm−1 on a Bruker ALPHA FT-IR spectrometer equipped with attenuated total reflectance (ATR) sampling unit. The resolution of the instrument was 0.9 cm−1, and 128 scans were used.
\nConductivity data were collected by using AC impedance spectroscopy. A Solartron 1250 frequency response analyzer, along with a home-built current-preamplifier circuit was utilized. The amplitude of the sine wave perturbation was 50 mV, and a frequency range from 10 kHz to 0.01 Hz was used. The samples were run as cast films on rectangular glass substrates. Silver paste was placed on the two ends of the films as electrodes, so that current flow was along the film, parallel to the substrate. Prior to the conductivity measurements, samples were held in vacuum for at least 20 h at room temperature to remove any moisture and adsorbed volatile materials. During conductivity measurements, the samples remained in vacuum and were in thermal contact with an electrically heated copper sample holder cooled by a Cryodyne 350 refrigerator. A Lakeshore Cryotronics Model 321 temperature controller was used for temperature regulation. After the conductivity measurements, the glass substrates were cleaved so that the film thickness could be measured with an optical microscope.
\nPowder XRD patterns were used to confirm the successful intercalation of POEGO and Li-POEGO into V2O5
XRD of (a) V2O5
Materials (ratios) | \nObserved | \nExpansion Δ | \nAverage crystallite size (Å) | \n
---|---|---|---|
V2O51.9H2O | \n11.9 | \n– | \n73 | \n
V2O5MeOH | \n14.5 | \n2.6 | \n89 | \n
V2O5POEGO (1:0.5) | \n17.9 | \n6.0 | \n79 | \n
V2O5POEGO (1:1) | \n20.4 | \n8.5 | \n96 | \n
V2O5POEGO (1:2) | \n20.8 | \n8.9 | \n85 | \n
V2O5POEGO (1:3) | \n20.6 | \n8.7 | \n97 | \n
V2O5POEGO (1:4) | \n21.0 | \n9.1 | \n70 | \n
List of interlayer expansions and average crystallite size of the nanocomposites.
The XRD patterns of the nanocomposites showed complete intercalation of POEGO in the gallery space of the host, based on the absence of the pristine V2O5
\nTable 1 shows that there is no significant increase in
From the XRD patterns, the average crystallite size of the nanomaterials was calculated by using the Scherrer equation. The Scherrer equation is
All the nanocomposite mole ratios prepared formed homogeneous solutions that were cast into thin films for XRD and conductivity studies. However, upon freeze-drying, the solutions from mole ratios 1:3 and 1:4 separated into two solid phases. One phase was a fine powder and the other phase was a sticky mass. The two phases were characterized separately with the other techniques (TGA, DSC, and FTIR).
\nThe thermostability and stoichiometric composition of the nanocomposites were determined using TGA data. Figure 2 shows the decomposition profile for POEGO, V2O5MeOH, V2O5POEGO 1:1, and V2O5POEGO 1:4 (the fine powder and the sticky mass). The thermograms were obtained in air using a heating rate of 10°C min−1. POEGO decomposed completely in air, as shown in Figure 2, curve a. The control sample (V2O5MeOH) has the highest residue percentage of 89% as shown in Figure 2, curve e. Curves b and c of Figure 2 show the decomposition profiles for V2O5POEGO 1:4 (sticky mass) and V2O5POEGO 1:4 (fine powder), respectively, while that of V2O5POEGO 1:1 is depicted by curve d. A complete analysis of the TGA data is summarized in Table 2. The nanocomposites have a weight residue percentage that corresponds to the amount of V2O5
TGA of (a) POEGO, (b) V2O5POEGO 1:4 sticky mass (c) V2O5POEGO 1:4 powder, (d) V2O5POEGO 1:1, and (e) V2O5MeOH.
Material | \nDecomposition in air | \nResidue (wt.%) | \n||
---|---|---|---|---|
Mole ratios used | \nComposition ratios | \nWeight (%) | \nTemperature (°C)2 | \n|
POEGO | \n\n | 100 | \n291 | \n0 | \n
V2O5 | \nV2O5(H2O)1.9 | \n10.3, 2.5 | \n49; (321, 364) | \n84.3 | \n
V2O5MeOH | \nV2O5(MeOH)0.7 | \n8.4 | \n80 | \n88.8 | \n
V2O5POEGO (1:0.5) | \nV2O5(POEGO)0.1(H2O)0.8 | \n22.3 | \n285 | \n72.2 | \n
V2O5POEGO (1:1) | \nV2O5(POEGO)0.3(H2O)1.8 | \n36.8 | \n248 | \n53.5 | \n
V2O5POEGO (1:2) | \nV2O5(POEGO)0.6(H2O)1 | \n55.7 | \n204 | \n40.2 | \n
V2O5POEGO (1:3) f | \nV2O5(POEGO)0.6(H2O)0.7 | \n59.0 | \n(205, 254) | \n38.1 | \n
V2O5POEGO (1:3) s | \nV2O5(POEGO)1.1(H2O)3.2 | \n68.2 | \n209 | \n24.1 | \n
V2O5POEGO (1:4) f | \nV2O5(POEGO)0.4(H2O)0.3 | \n49.6 | \n(195, 245) | \n48.6 | \n
V2O5POEGO (1:4) s | \nV2O5(POEGO)1.2(H2O)0.6 | \n72.9 | \n260 | \n25.5 | \n
TGA data for POEGO, V2O5
Note. "f" denotes the fine powder phase and "s" denotes the sticky mass phase.
The thermogram of the control sample (Figure 2, curve e) shows a constant weight residue above 100°C, that is, after the evaporation of methanol. Therefore, the weight loss process above 100°C for the nanocomposites is associated with the polymer decomposition (see Figure 2). Increasing the amount of POEGO in the nanocomposites decreases the residue percentage, due to the decreased concentration of V2O5
For the nanocomposites which separated into two phases, the fine powder phases (Figure 2, curve c) yielded higher residue percentages compared to the corresponding sticky mass phases (Figure 2, curve b). These data mean that the sticky phases have higher polymer component than the fine powder. Interestingly, the residue percentages of the sticky phases have similar weight percentages of 24.1% and 25.5% for V2O5POEGO 1:3 and V2O5POEGO 1:4, respectively. On the other hand, the corresponding residue percentages of the fine powders are significantly different, having a difference of more than 10%. This observation means that during the phase separation, the composition of the sticky phase is independent of the amount of V2O5
The decomposition profiles can be divided into three stages as shown in Figure 2. In stage I (<120°C), the weight loss corresponds to the evaporation of water/solvent. The weight loss in stage I varies randomly with no correlation to the amount of polymer used. In stage II (120–400°C), the weight loss corresponds to the decomposition of the polymer. At this stage, the percentage weight loss is directly proportional to the amount of the polymer present in the nanocomposite. Finally, stage III (>400°C) corresponds to the residue which has a constant weight percentage. The residue, yellow in color, was identified with XRD to be orthorhombic V2O5 crystals. 2 The temperature values were taken from the peak maximum of the derivative plot. Where the derivative peaks were not well resolved (due to overlapping weight loss steps), the temperature values of the peaks are enclosed in brackets.
The stoichiometric compositions were calculated based on the mass loss at each of the first two stages, the mass of the residue, and the corresponding molecular weight of the compound. The mass loss at stage I, stage II, and the mass of the residue (stage III) were assumed to correspond to water, POEGO, and V2O5, respectively. The moles of water, POEGO, and V2O5 were calculated for each sample. The mole ratios were expressed with respect to the moles of V2O5 (e.g., the composition for V2O5POEGO 1:1 was determined to be V2O5(POEGO)0.3(H2O)1.8).
DSC provided important information on
DSC of (a) POEGO, (b) V2O5POEGO 1:1, (c) V2O5POEGO 1:4 fine powder, and (d) V2O5POEGO 1:4 sticky mass at a scan rate of 10°C min−1 (
Materials (mole ratio) | \nPhase transitions | \nΔ | \n|
---|---|---|---|
POEGO | \n−52.2 | \n– | \n– | \n
V2O5POEGO (1:1) | \n−25.9 | \n99 | \n124.9 | \n
V2O5POEGO (1:2) | \n−25.2 | \n108 | \n133.2 | \n
V2O5POEGO (1:3) f | \n−30.4 | \n115 | \n145.4 | \n
V2O5POEGO (1:3) s | \n−35.3 | \n113 | \n148.3 | \n
V2O5POEGO (1:4) f | \n−30.0 | \n115 | \n145.0 | \n
V2O5POEGO (1:4) s | \n−31.6 | \n116 | \n147.6 | \n
DSC thermal transitions for POEGO and nanocomposites.
Note. “f” denotes the fine powder phase and “s” denotes the sticky mass phase.
All samples show negative sloping baselines after the glass transition temperature, which indicates the slow heat flow to the sample, which may correspond to the energy used to vaporize volatiles from the samples during heating. The horizontal baseline displayed by the sticky phase (Figure 3, curve d) means that the sample and the reference cell are in thermodynamic equilibrium. This observation is characteristic for amorphous and flexible materials [26].
\nThe blending temperature being below the decomposition temperature (<200°C) means that thin films can be obtained by hot pressing the fine powder or the sticky mass up to 100°C, without any decomposition or damage.
\nThe DSC comparison between POEGO (Figure 3, curve a) and V2O5POEGO 1:4 sticky mass phase (Figure 3, curve d) showed that the sticky mass phase did not have any crystallization or melting
The temperature gap (Δ
FTIR spectroscopy was used to investigate the type of chemical bonds present in the nanocomposites in comparison to POEGO and pristine V2O5
FTIR spectrum for (a) POEGO, (b) V2O5
It is important to note that comparison of the IR spectra for V2O5
The absorption bands for C=O and V=O were significantly perturbed in the nanocomposites, an indication for a chemical reaction between POEGO and V2O5
The impedance experiment involved applying an AC voltage to the sample and measuring the real and imaginary parts of the resulting current. Curve (a) in Figure 5 is a complex plane plot of the impedance of a Li-POEGO cast-film sample at a temperature of 310 K. High-frequency data is near the origin. A semicircle like this, with a low-frequency diagonal spur on the right, is characteristic of an ionic conductor between blocking electrodes [28]. Also shown is a fit to the equivalent-circuit model shown in the inset in Figure 5. In this circuit,
(a) Complex plane plot of the impedance of Li-POEGO at 310 K. The line is a fit to the equivalent circuit shown in the inset. (b) Impedance data for V2O5POEGO 1:4 at 300 K.
Impedance data for a typical nanocomposite, V2O5POEGO 1:4 (batch EM1-77), at 300 K, is also shown in Figure 5 (curve b). The plots for all our nanocomposites are semicircles, similar to the plots for a simple parallel RC circuit, indicating that the nanocomposites are electronic conductors. Here,
Electronic conductivity data for V2O5
Temperature-dependent conductivities of V2O5
The results for the nanocomposite samples from sample group EM1-33, which were all made at the same time, using the same V2O5
Conductivities of a few V2O5LiPOEGO nanocomposites were also measured, and one typical sample is included in Figure 6. In general, the electrical conductivity of V2O5LiPOEGO was less than that of V2O5POEGO. We were not able to detect any signs of ionic conductivity in the V2O5LiPOEGO nanocomposites. However, with the impedance technique used in this work, if the ionic conductivity is much smaller than the electronic conductivity, it will not be detected. A material like V2O5LiPOEGO 1:4 is expected to conduct lithium ions, and these experiments do not rule that out, since as long as the ionic conductivity is below about 10−5 S/cm at 300 K, we would not be able to observe it.
\nWhen conductivity data plot as straight lines in an Arrhenius-type plot like Figure 6, this indicates a thermally activated conduction process described by an equation of the form
where
Note that the band gap does not depend on the V2O5:POEGO ratio. Our XRD data shows that interlayer expansion is also almost independent of V2O5:POEGO ratio, indicating that the interlayer spaces are fully occupied with a bilayer arrangement of POEGO chains even before the ratio reaches 1:1. Since increasing the amount of POEGO further does not result in more POEGO between the V2O5 layers, some of the POEGO must be outside the nanocomposite crystallites. This interpretation of the XRD data explains two features of the conductivity. First, assuming the increase in activation energy is due to separation of the V2O5 layers and/or interaction between the V2O5 layers and the inserted polymers, there should be no further change in activation energy once the interlayer spaces are full. Second, as the amount of POEGO is increased beyond what is needed to fill the interlayer spaces, regions of electrically insulating polymer will form outside the nanocomposite crystallites, blocking some charge-transport channels and reducing the conductivity through the sample.
\nSince the conductivity measurements were made with cast films in which phase separation does not occur, we have not yet acquired the conductivity data on the separate fine powder and sticky mass phases obtained from freeze-dried V2O5POEGO 1:3 and V2O5POEGO 1:4. Characterization of charge transport in these phases would be an interesting topic for future work. Because of the high polymer content in the sticky mass phase, complexing it with a lithium salt may yield a material with higher ionic conductivity.
\nIn summary, successful intercalation of POEGO and Li-POEGO into V2O5
The authors are grateful for the financial support from the Natural Sciences and Engineering Research Council (NSERC) of Canada, Canada Foundation for Innovation (CFI), Atlantic Innovation Fund of Canada (AIF), Innovation Prince Edward Island (PEI), and University of Prince Edward Island (UPEI).
\nSexual dimorphism is characterized by morphological and physiological changes driven by sex steroids. In the rodent brain, it occurs during a critical period characterized by higher plasticity of neurons allowing changes in neuronal circuits and connectivity. For instance, hormonal manipulation during this time window, such as castration in males or replacement therapy in females (injections of androgen or estrogen), resulted in the conversion of intrinsic features and alteration of structures and functions of neural circuits in the brain. In rodents, critical time span for brain sex differentiation extends from embryonic day (ED) 18 to the postnatal day 10 [1], while in human it is exclusively embryonic day (ED12–22). Post this critical period, neuronal plasticity is lost and the effects of sex steroids can be diverted to activational effects in the brain. The mechanisms involved in defining the timing and duration of the neonatal critical period for the brain sexual differentiation remains to be determined. It is proposed that epigenetic modifications such as DNA methylation and histone acetylation might control the expression of genes implicated in brain sexual dimorphism [2].
The neuroendocrine systems, which control the action of sex steroids, including that on neural circuits, are differentiated in a sex-dependent manner, resulting in the regulation of reproductive and sex-specific behaviors. The actions of sex steroids in masculinization and feminization of the brain are mediated by steroid hormone receptors. In both human and nonhuman primates, young male and females show sex differences in toy preferences [3, 4]. Girls with congenital adrenal hyperplasia (CAH) show to preference toward toys of males and to have decreased female-typical behavior [5]. These results argue that behavioral sex differences are caused by sex steroids. Estrogen is produced locally in the brain from testosterone by the aromatase cytochrome P450 enzyme [6, 7] and affects sexual differentiation by biding to estrogen receptor (ER) in rodents. Maternal and fetal estrogen can be bound by the α-fetoprotein produced by fetal liver cells and yolk-sac cells, thereby preventing their passage through the blood–brain barrier [8]. This mechanism results in female brain being free from estrogen. In contrast, in males, testosterone crosses the blood–brain barrier and is converted by aromatase to elicit sexual differentiation of the brain [6, 7, 9]. The effects of testosterone and its enzymatic derivative, estradiol, on their receptors are therefore critical for the sexual differentiation of the brain.
The crucial role of estrogens in the sexual differentiation of the brain is mediated by estrogen receptors subtypes ERα [10, 11] and ERβ [12]. The amount of steroid hormone receptors differentiated and available development differs between sexes. The anteroventral periventricular nucleus (AVPV) is greater in size and cell number in females than in males [13, 14]. In the AVPV, the distribution of ERα is similar in both sexes, but its expression levels are higher in females than in males in prepubertal and adult rats [15]. In contrast, the distribution pattern for ERβ detected by nonisotopic
Sexual dimorphism in the AVPV. ERβ positive cells aggregated densely in females (A-C), whereas the ERβ-containing cells in males (D-F) dispersed more laterally in the AVPV in the AVPV. Scale, 100 μm. From [
Steroid-mediated organization of the brain might involve cell apoptosis, cell migration, neurogenesis, cell differentiation and synaptogenesis. Estrogen and androgen induce programmed cell death [17] by the sequential activation of cysteine-dependent asparate-specific proteases (caspase) during the development of the hypothalamus [18] in the dimorphism of dopaminergic neurons in the AVPV [19, 20, 21]. The total number of ERβ-positive cells within the AVPV is not different between intact females and males [15, 22]. This is assumed to be caused by mechanisms other than apoptosis namely the sexual dimorphic expression of ERβ in the AVPV. The sexual dimorphic features of the brain caused by sex steroids do not always coincide with larger nuclei exclusively in one sex. Indeed, a region-specific ERβ gene expression is observed in the AVPV [22]. Moreover, the steroids might act on specific regions in the brain [22]. In brain slices from developing mouse brain, estradiol but not dihydrotestosterone induces and modulates neuronal migration [23, 24]. These results suggest that sexual dimorphism of ERβ in the AVPV might contribute to migration rather than apoptosis or neurogenesis.
In the AVPV of female rats, a majority of ERβ-positive cells also express ERα [16]. It has been shown that ERα together with kisspeptin regulates ovulation, while ERβ is rather modified by these events [25]. At the molecular level, ERs bind to an estrogen responsive element (ERE) [26] after heterodimer formation [27], which allows the integration and collaboration of various signaling pathways for the completion of ovulation. The experimental infusion of antisense oligonucleotides in females results in decreased ERβ expression in the AVPV and consequently a persistent estrous [16]. Moreover, ERβ-positive cells and dopaminergic neurons have comparable distribution patterns in the AVPV [16]. Both ERα and ERβ have a role in the sexual dimorphism of dopaminergic neurons in the AVPV in both sexes [16, 28]. The secretion of luteinizing hormone (LH) is controlled by dopaminergic projections to neurons producing the gonadotropin-releasing hormone (GnRH) [29]. The cycle of female rats stalls ovulation state by small lesions of the AVPV [30]. Altogether, these data suggest that ERα and ERβ are colocalized with GnRH and are involved in LH secretion [31, 32]. In particular, ERα exerts a positive role for GnRH neurons, while ERβ exerts a negative control of those neurons [25]. Nonclassical ERE-independent ERα effects are involved in negative regulation on pulsatile GnRH secretion, while ERβ effects are involved in positive regulation on that secretion [31, 33]. It is still controversial to regulate GnRH neurons by ERs. Considering the inherent male distribution pattern of ERβ, a peculiar characteristic of the dopaminergic innervation in the AVPV [28] might be responsible for the GnRH secretion in the brain of males.
The sexually dimorphic nucleus in the preoptic area (SDN-POA) was first characterized by Nissl staining, revealing in a larger volume in the brain of male rats than that in the brain of female rats [1, 34]. The volume of this nucleus is altered by gonadal steroids during the perinatal critical period [1]. Somatostatin might also be involved in sexual dimorphism in the SDN-POA. Indeed, during development, cells positive for somatostatin are expressed in a sex-dependent manner in the SDN-POA. Sex reversal of the dimorphism of somatostatin expression is observed in orchidectomized males and estrogen treated female pups [35]. The somatostatin mRNA-positive cells are significantly more in males than in females, but eventually the difference recedes. Somatostatin expression in females is steady during the postnatal development. The transcription of somatostatin is transient and seems to contribute to the development of the SDN-POA. Somatostatin might prompt neuronal differentiation and survival via the somatostatin receptor.
Immunostaining against calbindin D28k, a major cytoplasmic calcium-binding and buffering protein, has been successfully used to identify the rat hypothalamus [36], SDN-POA [35, 37] and provides an alternative to Nissl staining [37]. Distribution of calbindin-labeled cells in the SDN-POA is similar to somatostatin in both sexes. It has been suggested that apoptosis has a role in sexual differentiation of the SDN-POA [38]. However, no difference in the total numbers of calbindin positive cells was observed in the SDN-POA after perinatal administration of bromodeoxyuridine in both sexes [39]. On the contrary, in the postnatal SDN-POA, these neurons still show an aggregated distribution in females, while they are dispersed laterally in males [39]. Altogether, these data suggest that, besides apoptosis, cell proliferation and migration might contribute to the morphological difference in the rat SDN-POA. Moreover, ERα are reported to be expressed in the SDN-POA [40], suggesting the presence of estrogenic action in the SDN-POA sexual dimorphism.
Moreover, Nissl stained SDN-POA had not been reported in mouse until recently identified by calbindin immunohistochemistry [41] (Figure 2). The morphological sex-dependent differences of the mouse SDN-POA were first demonstrated and established in terms of morphology and linked to gonadal steroid hormones during the prenatal critical period. Male mice have a greater number of calbindin-positive cells than females [41]. Similar differences within medial POA/anterior hypothalamic area (AHA) are observed in sheep, which are smaller in females than in males [42]. The volume of this nucleus in males is smaller in male-oriented than in female-oriented individuals. In humans, interstitial nuclei of the anterior hypothalamus (INAH) are considered comparable to those of rodent and sheep. The INAH is smaller in females than in males and smaller in homosexual men than in heterosexual men [43]. These results suggested that the sexual dimorphic nucleus in the two species is involved in sexual orientation. The male mice copulatory behavior and the preference for females is attributed to this difference in the SDN-POA [44, 45, 46, 47]
Sexual dimorphism in the SDN-POA. Calbindin (CB)-immunoreactive cells in the mouse SDN-POA in males (A-E) and in females (F-J) in the rostral-caudal direction. In males (B-D), but not females, a cell aggregate of CB-positive cells is prominent. Sale, 400 μm. From [
In the preoptic area (POA), ERα expression is much higher in females than in males [48]. This sex difference occurs during the perinatal period. After birth, the expression of ERs is down regulated in the POA by estrogen [49]. The decreased ERα expression occurs in both sexes but the differential expression in the POA between females and males persists throughout life. Although the ERα levels are higher in females than in males, a comparable distribution pattern of ERα is observed [16, 48]. The POA has been implicated to be involved in steroid activation of the male copulatory behavior [50]. In particular, dopamine neurons in the mPOA prompt male sexual behavior [51]. ERα and oxytocin containing neurons in the mPOA participate to control copulatory behavior in male rats [52, 53, 54]
Schematic representation of the distribution of ERβ mRNA-positive cells in the forebrain of rats through rostrocaudal axis. Scale, 100 μm. AC, anterior commissure; AVPV, anteroventral periventricular nucleus; BST, bed nucleus of the stria terminals; Fx, fornix; MPN, medial preoptic nucleus; OC, optic chiasm; SCN, suprachiasmatic nucleus; V3, third ventricle. From [
The volume of the ventromedial hypothalamus (VMH) is larger in males than in females [62, 63]. ERα and ERβ are expressed in the VMH of rodents [22, 48]. However, ERα expression is abundant in the ventrolateral portion of the VMH and is higher in female rats than in male rats [48]. The sex difference is most likely due to the conversion of testosterone into estrogen, which downregulates ERα expression. Moreover, the aromatase signal in males is more robust than in females [64]. A sex difference in ERβ expression is observed in both postnatal day 14 and in the adult rat brain, indicating that the sexual dimorphism is also maintained throughout life [22]. ERβ expression in the adult VMH is downregulated by estrogen or testosterone administration. The difference in expression is reversed by administration of estrogen in female rats or orchidectomy male rats. This sexual dimorphism is entirely attributable to the effects of sex steroids on the brain organization and plasticity during the critical neonatal period of the brain. Estrogen, converted from circulating androgen in males, downregulates ERα and ERβ expression in the VMH [22, 48] and consequently physiological functions. Estrogen together with progesterone in the VMH induces female sexual reproductive behavior such as lordosis, sexual receptivity and odor preference [65].
In adult males, the expression of ERα is lower than that in females. Cells in the male VMH are activated during fighting [66]. In these processes, ERα is involved in sexual [67] and aggressive behaviors in mice [68, 69], whereas ERβ is assume to be inhibitory to the aggressive behavior [68]. Other studies have demonstrated that male sexual behavior is not affected by ERβ in the VMH [70], but is profoundly regulated by ERα and the androgen receptor (AR), suggesting a possible distinct role for ERβ and ERα on each behavior. Opposing social behaviors, such as mounting and attack, are regulated by ERα [67] or progesterone receptor [71] cells located in discrete regions of the VMH. Sex steroid receptor expression in the VMH is induced by environmental hormonal milieu during the critical period and in turn controls the dynamic action of the sex hormones on sex-specific behavior in adults [66, 72]. These data suggest that males and females seem to exhibit identical neural circuits in the VMH, but the activated receptors might contribute to inducing the sex-typical behavior. The sex-specific neural circuit dictated by sex steroids could work in conjunction with estrogen-mediated ERs.
The medial amygdala (MeA) is larger volume in males than in females [73] and this difference is abolished after castration in males and androgen treatment in females [74]. In adults, the size and volume of neurons is modified by circulating androgen. After castration of adult male rats, the cell soma size in the posterodorsal MeA (MePD) is similar to the one observed in females [74]. However, the number of MeA neurons in both sexes is not affected by adult androgens [75]. Steroid hormones also influence the organization of the MePD during the neonatal period [76, 77] and its metabolite, estrogen, results in masculinization of the MePD. ERα and ERβ are abundantly expressed in the MePD [22, 48, 78, 79] where the aromatase enzyme is also detected [80, 81]. ERs mediate estrogen-induced modifications in the MePD associated with masculinization and male-specific behaviors [82]. However, the masculinization in the MePD in the adult brain is mostly driven by circulating androgen [82]. Both the action of ER [82] and AR [83] in the MePD on the size of neuronal somas and in the sexual behavior mostly occurs in the adults [82]. In adults, there is no sex-dependent difference in ER subtype and expression in the MePD, but there is a sexual dimorphic expression of ERβ but not ERα in newborns [84]. Neonatal hormonal manipulations could not reverse the sex differences in ERβ in both sexes, suggesting that ERβ-mediated estrogen actions are not involved in the sexual dimorphism in the MePD. Furthermore, ERβ is highly expressed in the MePD of adult female and male rats and is not affected by gonadectomy or estrogen treatment in both sexes [22]. Therefore, the ERβ expression also acts independent of activity in this structure.
In the MePD, sexual dimorphism involves mechanisms distinct from other regions of the brain. The MePD receives inputs from the olfactory and pheromonal systems, suggesting a functional role of this structure in sex arousal and regulation of adult social behaviors, including mating, aggressive [85, 86], and territorial behavior [87]. Acquisition of mating stimuli induces Fos in the ERs in the MeA [88]. Finally, the mechanisms induced by the ERs in the MeA and those involved in sexual stimuli [89], gonadotropin secretion [90], ovulation [91] sex and courtship behaviors [87], onset of puberty [92], parenting, and reproduction [85, 89, 93] still remain to be identified.
Sexual dimorphism is characterized by morphological differences in several regions of the brain. Morphological sex differences in the POA/AHA and the INAH were revealed in sheep and human brains, which are assumed to be important for determining sexual orientation. Expression of the phenotypes i.e., behavioral sex differences, are suggested to be derived from morphological sex differences in the brain. However, the morphological sex differences are subtly evident in other human brain regions; hence, their association with functional sex differences in the human brain remains controversial. Consequently, CAH results in masculinized female brain, thereby leading to male-typical preferences, which are the congenital characteristics inherently caused by steroid and not acquired by learning. Striking sex differences in animal models contribute in establishing the mechanisms of sexual dimorphism in the brain of all living beings.
ER expression levels contribute substantially to the physiological and behavioral differences. However, the extent to which the amounts of ER control the development of sexual dimorphism remains to be clarified. Sex-specific neural circuits activated by sex steroids might contribute to the functional role of ERs activated by estrogens. Recently it was evidenced that a high neuronal plasticity rate in neural circuits is necessary to ensure precise sex-specific responsiveness to sex steroids. The mechanism involved in the regulating the local action of sex steroids remains to be elucidated. Particularly, the expression and regulation of genes implicated in sexual dimorphism must be investigated.
This work was supported, in part, by grants-in-aid for scientific research from the Japanese Ministry of Education, Science, Sports and Culture [19 K12738 (2019-2021)] (C.O.).
None.
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\nIn the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
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\\n\\nWe started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\nIn the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n2004
\n\n2005
\n\n2006
\n\n2008
\n\n2009
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