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Sexual Differentiation (sexual + differentiation)
Selected AbstractsSexual Differentiation of Behaviour in Monkeys: Role of Prenatal HormonesJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2009K. Wallen The theoretical debate over the relative contributions of nature and nurture to the sexual differentiation of behaviour has increasingly moved towards an interactionist explanation that requires both influences. In practice, however, nature and nurture have often been seen as separable, influencing human clinical sex assignment decisions, sometimes with disastrous consequences. Decisions about the sex assignment of children born with intersex conditions have been based almost exclusively on the appearance of the genitals and how other's reactions to the gender role of the assigned sex affect individual gender socialisation. Effects of the social environment and gender expectations in human cultures are ubiquitous, overshadowing the potential underlying biological contributions in favour of the more observable social influences. Recent work in nonhuman primates showing behavioural sex differences paralleling human sex differences, including toy preferences, suggests that less easily observed biological factors also influence behavioural sexual differentiation in both monkeys and humans. We review research, including Robert W. Goy's pioneering work with rhesus monkeys, which manipulated prenatal hormones at different gestation times and demonstrated that genital anatomy and specific behaviours are independently sexually differentiated. Such studies demonstrate that, for a variety of behaviours, including juvenile mounting and rough play, individuals can have the genitals of one sex but show the behaviour more typical of the other sex. We describe another case, infant distress vocalisations, where maternal responsiveness is best accounted for by the mother's response to the genital appearance of her offspring. Taken together, these studies demonstrate that sexual differentiation arises from complex interactions where anatomical and behavioural biases, produced by hormonal and other biological processes, are shaped by social experience into the behavioural sex differences that distinguish males and females. [source] Initiation of Steroidogenesis Precedes Expression of Cholesterologenic Enzymes in the Fetal Mouse TestesANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 6 2009T. Büdefeld Summary Sexual differentiation is a carefully regulated process that ultimately results in a development of the male or female phenotype. Proper development of the male phenotype is dependent upon the action of testosterone and anti-mullerian hormone. Leydig cells start to produce testosterone around day 12.5 in the fetal mouse testis, and continue to produce high levels of this hormone throughout gestation. In the present study, we examined whether expression of lanosterol 14,-demethylase (cyp51) and cytochrome P450 NADPH reductase, both involved in the cholesterol production, occurs simultaneously with proteins required for the production of steroid hormones. Immunocytochemical staining with the antibodies against cyp51, cytochrome P450 NADPH reductase, steroidogenic acute regulatory protein (StAR) and 3beta-hydroxysteroid dehydrogenase I (3,-HSD I) was used to determine the ontogeny of expression of these four proteins. As expected, 3,-HSD I and StAR proteins were detected on day 12.5 p.c., while expression of cyp51 and NADPH cytochrome P450 reductase appeared 1 day later, on day 13.5. Thereafter, the expression of all four proteins remained strong throughout gestation. Results of this study suggest that initial steps of steroid hormone production in murine Leydig cells are mostly dependent on exogenously derived cholesterol, while from day 13.5 onwards, mouse Leydig cells are able to synthesize cholesterol and are therefore not dependent on exogenous cholesterol resources. [source] The androgenic gland and monosex culture of freshwater prawn Macrobrachium rosenbergii (De Man): a biotechnological perspectiveAQUACULTURE RESEARCH, Issue 3 2005Amir Sagi Abstract Males of the freshwater prawn Macrobrachium rosenbergii (De Man) grow faster and reach a larger size at harvest than females of the species. It is thus obvious that culture of monosex all-male populations would be economically advantageous. Sexual differentiation in crustaceans is regulated by the androgenic gland (AG), which plays a pivotal role in the regulation of male differentiation and in the inhibition of female differentiation. In M. rosenbergii, AG removal from immature males resulted in sex reversal, with complete female differentiation. Similarly, AG implantations into immature females lead to the development of the male reproductive system. Sex-reversed M. rosenbergii animals were capable of mating with normal specimens to produce offspring. Early attempts in Israel and more recently, attempts in other countries to establish all-male populations through manual segregation showed that for the production of monosex prawn populations to be economically feasible, intervention via the AG is probably required. However, a suitable biotechnology is still to be developed, and an androgenic hormone has yet to be identified in decapods. Three lines of aquacultural and biotechnological research and development are proposed for the future: (1) Establishment of monosex cultures through manual segregation, together with the application of selective harvesting and claw ablation, as well as examination of different monosex culture strategies under a variety of economic conditions. (2) Microsurgical intervention in the AG, leading to the development of functional neo-females, which would subsequently be mated with normal males to produce all-male progeny. (3) Elucidation of AG bioactive products to enable biochemical or molecular manipulation of sex differentiation. [source] Epigenetic abnormality of SRY gene in the adult XY female with pericentric inversion of the Y chromosomeCONGENITAL ANOMALIES, Issue 2 2010Tomoko Mitsuhashi ABSTRACT In normal ontogenetic development, the expression of the sex-determining region of the Y chromosome (SRY) gene, involved in the first step of male sex differentiation, is spatiotemporally regulated in an elaborate fashion. SRY is expressed in germ cells and Sertoli cells in adult testes. However, only few reports have focused on the expressions of SRY and the other sex-determining genes in both the classical organ developing through these genes (gonad) and the peripheral tissue (skin) of adult XY females. In this study, we examined the gonadal tissue and fibroblasts of a 17-year-old woman suspected of having disorders of sexual differentiation by cytogenetic, histological, and molecular analyses. The patient was found to have the 46,X,inv(Y)(p11.2q11.2) karyotype and streak gonads with abnormally prolonged SRY expression. The sex-determining gene expressions in the patient-derived fibroblasts were significantly changed relative to those from a normal male. Further, the acetylated histone H3 levels in the SRY region were significantly high relative to those of the normal male. As SRY is epistatic in the sex-determination pathway, the prolonged SRY expression possibly induced a destabilizing effect on the expressions of the downstream sex-determining genes. Collectively, alterations in the sex-determining gene expressions persisted in association with disorders of sexual differentiation not only in the streak gonads but also in the skin of the patient. The findings suggest that correct regulation of SRY expression is crucial for normal male sex differentiation, even if SRY is translated normally. [source] Influence of metyrapone treatment during pregnancy on the development and maturation of brain monoaminergic systems in the ratACTA PHYSIOLOGICA, Issue 4 2009M. L. Leret Abstract Aim:, This study examines the effect of reducing the corticosterone levels of gestating rat dams on the postnatal development and maturation of monoaminergic systems in their offspring's brains. Methods:, Metyrapone, an inhibitor of CORT synthesis, was administered to pregnant rats from E0 to E17 of gestation. Monoamine concentrations were determined in male and female offspring at postnatal days (PN) 23 and 90 in the hippocampus, hypothalamus and striatum. Results:, Reducing maternal corticosterone (mCORT) during gestation led to alterations in dopamine and serotonin levels in all three brain areas studied at PN 23. Alterations persisted until at least PN 90 in the serotonergic systems; the dopamine content of the hippocampus also remained modified. Reduced mCORT during gestation also led to alterations in the development and maturation of the hypothalamic noradrenergic systems. Sexually dimorphic responses were observed in all these monoaminergic systems at different times. Conclusion:, These results suggest that while they are still developing, brain monoaminergic systems are particularly sensitive to epigenetic influences. An adequate foetal level of CORT is required for the normal ontogeny of brain monoaminergic systems. The present data also provide that during the critical period of brain development, maternal CORT plays an important role in the sexual differentiation of monoaminergic systems, with particular influence on brain serotonergic neurones. [source] Sex-specific and left-right asymmetric expression pattern of Bmp7 in the gonad of normal and sex-reversed chicken embryosDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2 2005Anshin Hoshino A genetic switch determines whether the indifferent gonad develops into an ovary or a testis. In adult females of many avian species, the left ovary is functional while the right one regresses. In the embryo, bone morphogenetic proteins (BMP) mediate biological effects in many organ developments but their roles in avian sex determination and gonadal differentiation remains largely unknown. Here, we report the sex-specific and left-right (L-R) asymmetric expression pattern of Bmp7 in the chicken gonadogenesis. Bmp7 was L-R asymmetrically expressed at the beginning of genital ridge formation. After sexual differentiation occurred, sex-specific expression pattern of Bmp7 was observed in the ovary mesenchyme. In addition, ovary-specific Bmp7 expression was reduced in experimentally induced female-to-male reversal using the aromatase inhibitor (AI). These dynamic changes of expression pattern of Bmp7 in the gonad with or without AI treatment suggest that BMP may play roles in determination of L-R asymmetric development and sex-dependent differentiation in the avian gonadogenesis. [source] Androgen receptor gene expression in the developing and adult zebrafish brainDEVELOPMENTAL DYNAMICS, Issue 10 2008Daniel A. Gorelick Abstract Androgens play a central role in the regulation of male sexual differentiation and behavior in many vertebrates, including zebrafish. Their signaling is mediated by activation of the androgen receptor. A single androgen receptor (ar) gene was recently identified in zebrafish, which encodes a protein that binds androgens in vitro. However, the tissue-specific expression pattern of this receptor in vivo has not been described. Using whole-mount RNA in situ hybridization, we characterized expression of the ar gene in developing zebrafish and in the adult brain. In embryos, transcripts were found in the presumptive pronephros and in olfactory placodes. By 3,5 days postfertilization, ar transcripts were also detected in the pineal organ anlage and the retina. In the adult brain, ar was expressed in discrete regions of the telencephalon, in the preoptic area, and throughout the periventricular hypothalamus, regions previously implicated in the regulation of sexually dimorphic behaviors in mammals. Developmental Dynamics 237:2987,2995, 2008. © 2008 Wiley-Liss, Inc. [source] Sexual dimorphism of g-protein subunit Gng13 expression in the cortical region of the developing mouse ovaryDEVELOPMENTAL DYNAMICS, Issue 7 2007Akihiro Fujino Abstract In our search for genes required for the development and function of mouse gonads, we identified Gng13 (guanine nucleotide binding protein 13, gamma), a gene with an embryonic expression pattern highly restricted to the ovary. Based on reverse transcriptase-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization, Gng13 is expressed in both XX and XY gonads at embryonic day (E) 11.5, but becomes up-regulated in the XX gonad by E12.5. Expression is retained after treatment with busulfan, a chemical known to eliminate germ cells, pointing to the soma as a site of Gng13 transcription. In situ hybridization of embryonic ovarian tissue sections further localized the expression to the cortex of the developing XX gonad. Gng13 expression in the adult is also highly restricted. Northern blot analyses and Genomic Institute of the Novartis Research Foundation expression profiling of adult tissues detected very high expression in the cerebrum and cerebellum, in addition to, a weaker signal in the ovary. Gng13 belongs to a well-known family of signal transduction molecules with functions in many aspects of development and organ physiology. Here, we report that, in the developing mouse embryo, expression of Gng13 mRNA is highly restricted to the cortex of the XX gonad during sexual differentiation, suggesting a role for this gene during ovarian development. Developmental Dynamics 236:1991,1996, 2007. © 2007 Wiley-Liss, Inc. [source] The role of cell death in sexually dimorphic muscle development: Male-specific muscles are retained in female bax/bak knockout miceDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2008Dena A. Jacob Abstract The bulbocavernosus (BC) and levator ani (LA) muscles are present in males but absent or severely reduced in females, and the fate of these muscles controls the survival of motoneurons in the sexually dimorphic spinal nucleus of the bulbocavernosus. However, the mechanism underlying the sex difference in BC and LA development has been controversial. We examined the role of cell death in sexual differentiation of the bulbocavernosus BC/LA muscles in mice. Muscle development was mapped from embryonic day 16 (E16) to postnatal day 5 (P5). A sex difference (male > female) first arose on E17 (BC) or E18 (LA), and increased in magnitude postnatally. TUNEL labeling revealed dying cells in the BC and LA muscles of both sexes perinatally. However, females had a significantly higher density of TUNEL-positive cells than did males. A role for the proapoptotic factors, Bax and Bak, in BC/LA development was tested by examining mice lacking one or both of these proteins. In females lacking either Bax or Bak, the BC was absent and the LA rudimentary. Deletion of both bax and bak genes, however, rescued the BC, increased LA size ,20-fold relative to controls, and virtually eliminated TUNEL-positive cells in both muscles. We conclude that cell death plays an essential role in sexual differentiation of the BC/LA muscles. The presence of either Bax or Bak is sufficient for cell death in the BC/LA, whereas the absence of both prevents sexually dimorphic muscle cell death. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] The sexually dimorphic expression of L7/SPA, an estrogen receptor coactivator, in zebra finch telencephalonDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2007Kelli A. Duncan Abstract Sex differences in the zebra finch (Taeniopygia guttata) brain are robust and include differences in morphology (song control nuclei in males are significantly larger) and behavior (only males sing courtship songs). In zebra finches, hormonal manipulations during development fail to reverse sex differences in song nuclei size and suggest that the classical model of sexual differentiation is incomplete for birds. Coactivators act to initiate transcriptional activity of steroid receptors, and may help explain why hormonal manipulations alone are not sufficient to demasculinize the male zebra finch brain. The present study investigated the expression and localization of L7/SPA (an estrogen receptor coactivator) mRNA and protein expression across the development of zebra finch song nuclei from males and females collected on P1 (song nuclei not yet formed), P10 (posthatch day 10, song nuclei formed), P30 (30 days posthatch, sexually immature but song nuclei formed and birds learning to sing), and adult birds (older than 65 days and sexually mature). Northern blot analysis showed a significant sex difference in P1 and adult L7/SPA mRNA expression while Western blot analysis also showed enhanced expression in the male brain at all age points. Both in situ hybridization and immunohistochemistry demonstrated that L7/SPA mRNA and protein were located in the song nuclei as well as expressed globally. Elevated coactivator expression may be a possible mechanism controlling the development of male song control nuclei, and coactivators such as L7/SPA may be important regulators of the masculinizing effects of estradiol on brain sexual differentiation. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Glutamate AMPA/kainate receptors, not GABAA receptors, mediate estradiol-induced sex differences in the hypothalamusDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2007Brigitte J. Todd Abstract Sex differences in brain morphology underlie physiological and behavioral differences between males and females. During the critical perinatal period for sexual differentiation in the rat, gonadal steroids act in a regionally specific manner to alter neuronal morphology. Using Golgi-Cox impregnation, we examined several parameters of neuronal morphology in postnatal day 2 (PN2) rats. We found that in the ventromedial nucleus of the hypothalamus (VMN) and in areas just dorsal and just lateral to the VMN that there was a sex difference in total dendritic spine number (males greater) that was abolished by treating female neonates with exogenous testosterone. Dendritic branching was similarly sexually differentiated and hormonally modulated in the VMN and dorsal to the VMN. We then used spinophilin, a protein that positively correlates with the amount of dendritic spines, to investigate the mechanisms underlying these sex differences. Estradiol, which mediates most aspects of masculinization and is the aromatized product of testosterone, increased spinophilin levels in female PN2 rats to that of males. Muscimol, an agonist at GABAA receptors, did not affect spinophilin protein levels in either male or female neonates. Kainic acid, an agonist at glutamatergic AMPA/kainate receptors, mimicked the effect of estradiol in females. Antagonizing AMPA/kainate receptors with NBQX prevented the estradiol-induced increase in spinophilin in females but did not affect spinophilin level in males. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Localization of estrogen receptor-, and -,mRNA in brain areas controlling sexual behavior in Japanese quailDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2006Krister Halldin Abstract Two estrogen receptors (ERs), denoted ER, and ER,, have been identified in humans and various animal species, including the Japanese quail. Estrogens play a key role in sexual differentiation and in activation of sexual behavior in Japanese quail. The distribution of ER, in the brain of male and female adult quail has previously been studied using immunohistochemistry, whereas in situ hybridization has been employed to study the distribution of ER, mRNA in males only. In this article, we used in situ hybridization to study the distribution of mRNAs for both ER, and ER, in brain areas controlling sexual behavior of Japanese quail. Our results show that both ER, mRNA and ER, mRNA are localized in areas important for sexual behavior, such as the preoptic area and associated limbic areas, in both males and females. Moreover, we found differences in distribution of mRNA for the two receptors in these areas. The results of this article support previously reported data and provide novel data on localization of ER mRNAs in adult quail brain of both sexes. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005 [source] Sex differences in progesterone receptor immunoreactivity in neonatal mouse brain depend on estrogen receptor , expressionDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2001Christine K. Wagner Abstract Around the time of birth, male rats express higher levels of progesterone receptors in the medial preoptic nucleus (MPN) than female rats, suggesting that the MPN may be differentially sensitive to maternal hormones in developing males and females. Preliminary evidence suggests that this sex difference depends on the activation of estrogen receptors around birth. To test whether estrogen receptor alpha (ER,) is involved, we compared progesterone receptor immunoreactivity (PRir) in the brains of male and female neonatal mice that lacked a functional ER, gene or were wild type for the disrupted gene. We demonstrate that males express much higher levels of PRir in the MPN and the ventromedial nucleus of the neonatal mouse brain than females, and that PRir expression is dependent on the expression of ER, in these regions. In contrast, PRir levels in neocortex are not altered by ER, gene disruption. The results of this study suggest that the induction of PR via ER, may render specific regions of the developing male brain more sensitive to progesterone than the developing female brain, and may thereby underlie sexual differentiation of these regions. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 176,182, 2001 [source] Reversibility of estrogenic sex changes in zebrafish (Danio Rerio),ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2009Mia G. Larsen Abstract Development of male zebrafish (Danio rerio) courtship behavior was studied following estrogenic disruption of sexual differentiation. Sixty zebrafish were exposed at 28C to 5 ng/L (nominal concentration) of 17,-ethinylestradiol (EE2) from the egg stage until adulthood at four months of age, resulting in a female-biased sex ratio. Twenty-five EE2 -exposed phenotypic female zebrafish were subsequently held in clean water for eight months. During this period, eight phenotypic males developed. These phenotypic males demonstrated significant behavioral aberrations and a low fertilization rate compared to control males. [source] Effects of 4-nonylphenol and 4- tert -octylphenol on sex differentiation and vitellogenin induction in medaka (Oryzias latipes)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2003Masanori Seki Abstract Medaka (Oryzias latipes) were continuously exposed to various concentrations of two alkylphenols, 4-nonylphenol (NP) and 4- tert -octylphenol (OP), from fertilized eggs to 60 d posthatch. The effects on sexual differentiation and hepatic vitellogenin (VTG) induction in medaka were assessed to elucidate the lowest-observed-effect concentrations (LOECs) of NP and OP for these events during early life stages. The LOECs of NP and OP for these events were 11.6 and 11.4 ,g/L, respectively. These results suggest that NP and OP may have adverse effects at similar concentrations during early life stage in medaka. Additionally, we investigated whether the abnormal sex differentiation induced by these alkylphenols would be permanent or reversible once the medaka were returned to clean water. The appearance of the secondary sex characteristics reverted from female to male when fish were returned to clean water. However, gonadal histology showed that intersex gonads still existed, even after the fish were transferred to clean water for two months. These results suggest that the induced feminization of secondary sex characteristics in medaka exposed to alkylphenols during the stage of sexual differentiation may not always be permanent, but the gonadal alteration (testisova) may continue much longer. [source] Reproductive and transgenerational effects of methylmercury or Aroclor 1268 on Fundulus heteroclitusENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2001Mary Baker Matta Abstract This research determined the potential for methylmercury or Aroclor 1268 to disrupt reproduction and sexual differentiation in Fundulus heteroclitus. The research determined whether fish that are exposed to mercury or Aroclor 1268 survive and successfully reproduce; whether offspring of exposed fish hatch, survive, produce eggs, and fertilize them; and whether the secondgeneration offspring of exposed fish hatch and survive. Fundulus heteroclitus were exposed to mercury or Aroclor 1268 via contaminated food. Endpoints evaluated included survival, growth, fecundity, fertilization success, hatch success, larval survival, sex ratios, and the prevalence of gonadal abnormalities. In general, polychlorinated biphenyls were highly bioavailable and accumulated well through feeding. The only statistically significant effect observed as a result of treatment with Aroclor 1268 was an increase in growth in the offspring of exposed fish. Mercury was accumulated in a dose-dependent fashion via food exposures. Exposure to mercury in food increased mortality in male F. heteroclitus, which possibly occurred as a result of behavioral alterations. Increased mortality was observed at body burdens of 0.2 to 0.47 ,g/g. Offspring of F. heteroclitus fed mercury-contaminated food were less able to successfully reproduce, with reduced fertilization success observed at egg concentrations of 0.01 to 0.63 ,g/g, which corresponds with parent whole-body concentrations of 1.1 to 1.2 ,g/g. Offspring of exposed fish also had altered sex ratios, with treatment at moderate concentrations producing fewer females and treatment at the highest concentration producing more females than expected. Alterations in sex ratios were observed at concentrations of less than 0.01 ,g/g in eggs or between 0.44 and 1.1 ,g/g in parents. Offspring of mercury-exposed fish also had increased growth in moderate treatments, when egg concentrations were less than 0.02 ,g/g, or when parent whole bodies contained 0.2 to 0.47 ,g/g. In summary, exposure to mercury reduced male survival, reduced the ability of offspring to successfully reproduce, and altered sex ratios in offspring. Both direct effects on exposed fish and transgenerational effects were observed. [source] Kisspeptin/GPR54 system as potential target for endocrine disruption of reproductive development and functionINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010M. Tena-Sempere Summary Kisspeptins, the products of Kiss1 gene acting via G protein-coupled receptor 54 (also termed Kiss1R), have recently emerged as essential gatekeepers of puberty onset and fertility. Compelling evidence has now documented that expression and function of hypothalamic Kiss1 system is sensitive not only to the activational effects but also to the organizing actions of sex steroids during critical stages of development. Thus, studies in rodents have demonstrated that early exposures to androgens and oestrogens are crucial for proper sexual differentiation of the patterns of Kiss1 mRNA expression, whereas the actions of oestrogen along puberty are essential for the rise of hypothalamic kisspeptins during this period. This physiological substrate provides the basis for potential endocrine disruption of reproductive maturation and function by xeno-steroids acting on the kisspeptin system. Indeed, inappropriate exposures to synthetic oestrogenic compounds during early critical periods in rodents persistently decreased hypothalamic Kiss1 mRNA levels and kisspeptin fibre density in discrete hypothalamic nuclei, along with altered gonadotropin secretion and/or gonadotropin-releasing hormone neuronal activation. The functional relevance of this phenomenon is stressed by the fact that exogenous kisspeptin was able to rescue defective gonadotropin secretion in oestrogenized animals. Furthermore, early exposures to the environmentally-relevant oestrogen, bisphenol-A, altered the hypothalamic expression of Kiss1/kisspeptin in rats and mice. Likewise, maternal exposure to a complex cocktail of endocrine disruptors has been recently shown to disturb foetal hypothalamic Kiss1 mRNA expression in sheep. As a whole, these data document the sensitivity of Kiss1 system to changes in sex steroid milieu during critical periods of sexual maturation, and strongly suggest that alterations of endogenous kisspeptin tone induced by inappropriate (early) exposures to environmental compounds with sex steroid activity might be mechanistically relevant for disruption of puberty onset and gonadotropin secretion later in life. The potential interaction of xeno-hormones with other environmental modulators (e.g., nutritional state) of the Kiss1 system warrants further investigation. [source] A mixture of seven antiandrogens induces reproductive malformations in ratsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2008Cynthia V. Rider Summary To date, regulatory agencies have not considered conducting cumulative risk assessments for mixtures of chemicals with diverse mechanisms of toxicity because it is assumed that the chemicals will act independently and the individual chemical doses are not additive. However, this assumption is not supported by new research addressing the joint effects of chemicals that disrupt reproductive tract development in the male rat by disrupting the androgen signalling pathway via diverse mechanisms of toxicity [i.e. androgen receptor (AR) antagonism in the reproductive tract vs. inhibition of androgen synthesis in the foetal testis]. In this study, pregnant rats were exposed to four dilutions of a mixture containing vinclozolin, procymidone, linuron, prochloraz, benzyl butyl phthalate, dibutyl phthalate and diethylhexyl phthalate during the period of sexual differentiation and male offspring were assessed for effects on hormone sensitive endpoints including: anogenital distance, infant areolae retention and reproductive tract tissue weights and malformations. The ratio of the chemicals in the mixture was based upon each chemical's ED50 for inducing reproductive tract malformations (hypospadias or epididymal agenesis). The observed responses from the mixture were compared with predicted responses generated with a toxic equivalency approach and models of dose addition, response addition or integrated addition. As hypothesized, we found that the mixture of chemicals that alter the androgen signalling pathway via diverse mechanisms disrupted male rat reproductive tract differentiation and induced malformations in a cumulative, dose-additive manner. The toxic equivalency and dose addition models provided the best fit to observed responses even though the chemicals do not act via a common cellular mechanism of action. The current regulatory framework for conducting cumulative risk assessments needs to consider the results, including those presented herein, which indicate that chemicals that disrupt foetal tissues during sexual differentiation act in a cumulative, dose-additive manner irrespective of the specific cellular mechanism of toxicity. [source] Prenatal testosterone treatment potentiates the aggression-inhibiting effect of the neurosteroid dehydroepiandrosterone in female miceAGGRESSIVE BEHAVIOR, Issue 2 2001Fabrice Perché Abstract The neurosteroid dehydroepiandrosterone (DHEA) is a powerful inhibitor of aggression in murine models when given for 15 days and potentially may be useful in the management of inappropriate human aggression. Although the biosynthesis and metabolism of DHEA have been described, little is known about the potential effect of the steroidal environment during sexual differentiation on the subsequent response to DHEA. Whether prenatal androgen exposure influences the subsequent response to DHEA was assessed by comparing the effect of DHEA (80 ,g/d) on aggression in female offspring where dams were treated with 1, 10, or 100 ,g of testosterone (T) on days 15 to 18 of gestation (Experiment I) or that developed in different uterine positions (Experiment II). The results showed that DHEA decreased attack behavior in general and that the 100-,g prenatal T treatments enhanced the antiaggressive effect of this neurosteroid. Neither the lower doses of exogenously administered T nor the uterine position led to an enhanced response to DHEA. In addition, whether DHEA produced changes in social and nonsocial activities was examined. In the 100-,g T females, DHEA increased the duration of the former and decreased the frequency and duration of the latter, indicating that it was not a general decrement in behavioral expression that mediated the enhanced response to the antiaggressive effect of DHEA. In the second experiment, DHEA treatment led to increased frequencies of social nonaggressive and nonsocial activities. However, the uterine positions × treatment interactions were not significant, demonstrating that contiguity to male fetuses did not differentially affect the response to DHEA. Aggr. Behav. 27:130,138, 2001. © 2001 Wiley-Liss, Inc. [source] Steroid-induced sexual differentiation of the developing brain: multiple pathways, one goalJOURNAL OF NEUROCHEMISTRY, Issue 5 2008Jaclyn M. Schwarz Abstract Hormone exposure, including testosterone and its metabolite estradiol, induces a myriad of effects during a critical period of brain development that are necessary for brain sexual differentiation. Nuclear volume, neuronal morphology, and astrocyte complexity are examples of the wide range of effects by which testosterone and estradiol can induce permanent changes in the function of neurons for the purpose of reproduction in adulthood. This review will examine the multitude of mechanisms by which steroid hormones induce these permanent changes in brain structure and function. Elucidating how steroids alter brain development sheds light on how individual variation in neuronal phenotype is established during a critical period. [source] Sex Differences and the Roles of Sex Steroids in Apoptosis of Sexually Dimorphic Nuclei of the Preoptic Area in Postnatal RatsJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2009S. Tsukahara The brain contains several sexually dimorphic nuclei that exhibit sex differences with respect to cell number. It is likely that the control of cell number by apoptotic cell death in the developing brain contributes to creating sex differences in cell number in sexually dimorphic nuclei, although the mechanisms responsible for this have not been determined completely. The milieu of sex steroids in the developing brain affects sexual differentiation in the brain. The preoptic region of rats has two sexually dimorphic nuclei. The sexually dimorphic nucleus of the preoptic area (SDN-POA) has more neurones in males, whereas the anteroventral periventricular nucleus (AVPV) has a higher cell density in females. Sex differences in apoptotic cell number arise in the SDN-POA and AVPV of rats in the early postnatal period, and an inverse correlation exists between sex differences in apoptotic cell number and the number of living cells in the mature period. The SDN-POA of postnatal male rats exhibits a higher expression of anti-apoptotic Bcl-2 and lower expression of pro-apoptotic Bax compared to that in females and, as a potential result, apoptotic cell death via caspase-3 activation more frequently occurs in the SDN-POA of females. The patterns of expression of Bcl-2 and Bax in the SDN-POA of postnatal female rats are changed to male-typical ones by treatment with oestrogen, which is normally synthesised from testicular androgen and affects the developing brain in males. In the AVPV of postnatal rats, apoptotic regulation also differs between the sexes, although Bcl-2 expression is increased and Bax expression and caspase-3 activity are decreased in females. The mechanisms of apoptosis possibly contributing to the creation of sex differences in cell number and the roles of sex steroids in apoptosis are discussed. [source] Sexual Differentiation of Behaviour in Monkeys: Role of Prenatal HormonesJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2009K. Wallen The theoretical debate over the relative contributions of nature and nurture to the sexual differentiation of behaviour has increasingly moved towards an interactionist explanation that requires both influences. In practice, however, nature and nurture have often been seen as separable, influencing human clinical sex assignment decisions, sometimes with disastrous consequences. Decisions about the sex assignment of children born with intersex conditions have been based almost exclusively on the appearance of the genitals and how other's reactions to the gender role of the assigned sex affect individual gender socialisation. Effects of the social environment and gender expectations in human cultures are ubiquitous, overshadowing the potential underlying biological contributions in favour of the more observable social influences. Recent work in nonhuman primates showing behavioural sex differences paralleling human sex differences, including toy preferences, suggests that less easily observed biological factors also influence behavioural sexual differentiation in both monkeys and humans. We review research, including Robert W. Goy's pioneering work with rhesus monkeys, which manipulated prenatal hormones at different gestation times and demonstrated that genital anatomy and specific behaviours are independently sexually differentiated. Such studies demonstrate that, for a variety of behaviours, including juvenile mounting and rough play, individuals can have the genitals of one sex but show the behaviour more typical of the other sex. We describe another case, infant distress vocalisations, where maternal responsiveness is best accounted for by the mother's response to the genital appearance of her offspring. Taken together, these studies demonstrate that sexual differentiation arises from complex interactions where anatomical and behavioural biases, produced by hormonal and other biological processes, are shaped by social experience into the behavioural sex differences that distinguish males and females. [source] Increased activity of factor VIII coagulant associated with venous ulcer in a patient with Klinefelter's syndromeJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2005J Dissemond ABSTRACT Klinefelter's syndrome is the most frequent major abnormality of sexual differentiation in men with two or more X chromosomes. Recurrent venous ulcers as a result of a post-thrombotic syndrome are a well known symptom in patients with Klinefelter's syndrome. Until now the underlying pathomechanisms are not completely understood. Platelet hyperaggregability, factor V Leiden mutation and abnormalities in fibrinolysis were implicated as possible contributing factors. Here we describe the detection of an increased activity of factor VIII coagulant (factor VIII:C). This is the first case report on increased factor VIII:C activity associated with venous ulcers in a patient with Klinefelter's syndrome. Elevated factor VIII plasma levels are gradually accepted to be associated with an increased risk for venous thromboembolism. Therefore, we discuss that the examination of factor VIII:C may help in clarifying individual thromboembolic risks, especially in patients with Klinefelter's syndrome. [source] The influence of social factors on adult sex change and juvenile sexual differentiation in a diandric, protogynous epinepheline, Cephalopholis boenak (Pisces, Serranidae)JOURNAL OF ZOOLOGY, Issue 3 2004Min Liu Abstract Adult sex change and juvenile sexual differentiation in the protogynous epinepheline Cephalopholis boenak were demonstrated in captivity to be influenced by social factors. Adult sex change in C. boenak occurred in two directions, female to male and male to female. The presence or absence of a larger male plays an important role in adult female sex change; female(s) did not change sex in the presence of a larger male, but sex change occurred after the removal of the larger males in the same social groups. In male pairs, either the larger or the smaller male changed sex. Male to female sex change has not been reported previously in Cephalopholis, and only rarely in epinephelines. This is the first report of direct male sexual differentiation from juveniles (i.e. primary male development), through manipulating the number of juveniles, in a protogynous epinepheline. All isolated, single, juveniles differentiated directly as males, and male to female sex ratios did not differ significantly from 1:1 in all experimental social groups of two to four juveniles. Differentiating males grew significantly faster than differentiating females and undifferentiated juveniles during the 57-week experimental period. The role of growth rate in sex determination in C boenak is not known but clearly plays a part in juvenile sexual differentiation and merits further investigation. Social factors influencing bi-directional adult sex change and juvenile sexual differentiation are a reflection of plasticity of sexual expression in C boenak, in particular, and the Serranidae in general. [source] Migration of human and mouse primordial germ cells and colonization of the developing ovary: An ultrastructural and cytochemical study ,MICROSCOPY RESEARCH AND TECHNIQUE, Issue 6 2006Jaime Pereda Abstract This review is an account of the origin and migratory events of primordial germ cells until their settlement in the gonad before sexual differentiation in the human as well as mice. In this context, the morphodynamic characteristics of the migration of the primordial germ cells, the macromolecular characteristics of the extracellular matrix of the migratory pathway, and the factors involved in the germ cell guidance have been analyzed and discussed in the light of recent advances in this field, by means of immunocytochemical procedures. The events prior to gonadal morphogenesis and the origin of the somatic cell content of the human gonadal primordium have been also analyzed. In particular, evidences are presented showing that cells derived from the coelomic epithelium and mesenchyme are at the origin of the somatic components of the gonadal primordium, and that a mesonephric cell contribution to the generation of somatic cell components of the genital ridge in humans should be discarded due to the morphological stability of the different nephric structures during the period preceding the sexual differentiation of the gonad. Microsc. Res. Tech., 2006. © 2006 Wiley-Liss, Inc. [source] Gender-related changes in the avian vasotocin system during ontogenyMICROSCOPY RESEARCH AND TECHNIQUE, Issue 1 2001Aleksandr Jurkevich Abstract The arginine vasotocin (AVT) system of the avian brain includes a sexually dimorphic part that extends from the caudal part of preoptic region through the medial part of the bed nucleus of stria terminalis (BSTm) to the lateral septum. It is composed of the parvocellular neurons located in the BSTm and the dense innervation of the medial preoptic region and lateral septum. In this part of the brain, AVT expression is stronger in males than in females in a few bird species investigated to date. This review focuses on the ontogeny of sexual differences in the vasotocinergic system of two gallinaceous species, domestic chicken and Japanese quail, and on the role of gonadal hormones in organizing during development and maintaining in adulthood these differences. Parvocellular AVT neurons become discernible in the BSTm of males and females during the second half of embryonic development. These cells undergo a profound and irreversible sexual differentiation during ontogenetic development. Recent findings demonstrate a dual role of estrogens in the organization and activation of sex differences in the AVT system. During the embryonic period of ontogeny, estrogens differentiate the AVT system in a sexually dimorphic manner in parallel with the differentiation of sexual behavior, while in adulthood estrogens, locally produced from testosterone in the male brain, activate AVT synthesis in the BSTm. The sexually dimorphic part of the AVT system is sensitive to a number of abiotic factors such as light, temperature, and water availability. It is suggested that sex dimorphic vasotocinergic systems could be implicated in processes of social recognition in various behavioral contexts. Microsc. Res. Tech. 55:27,36, 2001. © 2001 Wiley-Liss, Inc. [source] Zebra finch sexual differentiation: The aromatization hypothesis revisitedMICROSCOPY RESEARCH AND TECHNIQUE, Issue 6 2001Juli Wade Abstract Zebra finches have emerged as an outstanding model system for the investigation of the mechanisms regulating brain and behavior. Their song system has proven especially useful, as the function of discrete anatomical regions have been identified, and striking parallels exist between the morphology of these regions and the level of their function in males and females. That is, the structures are substantially more developed in males, who sing, compared to females, who do not. These parallels extend from higher (telencephalic) centers to the brainstem motor nucleus that innervates the muscles of the vocal organ. Other dimorphic aspects of reproduction in the zebra finch, such as copulatory behaviors and sexual partner preference, however, are not associated with known sex differences in anatomy. In many species, sex differences in neural and peripheral structures and behavior are regulated by secretions from the gonads, which of course are sexually dimorphic themselves. In birds, sex differences at all of these levels (gonad, brain, and behavior) can be mediated by steroid hormones. However, it is not entirely clear that gonadal secretions normally participate at all of the levels. This paper reviews the evidence relating to the role of gonadal steroids in the sexual differentiation of reproductive behaviors and the central and peripheral structures known to regulate them in zebra finches, with a focus on estradiol, which has been most extensively studied in the masculinization of song system morphology and function. Microsc. Res. Tech. 54:354,363, 2001. © 2001 Wiley-Liss, Inc. [source] High temperature causes masculinization of genetically female medaka by elevation of cortisolMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 8 2010Yuki Hayashi In poikilothermic vertebrates, sex determination is sometimes influenced by environmental factors such as temperature. However, little is known about the molecular mechanisms underlying environmental sex determination. The medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system. Recently, it was reported that XX medaka can be sex-reversed into phenotypic males by high water temperature (HT; 32,34°C) treatment during the sex differentiation period. Here we report that cortisol caused female-to-male sex reversal and that metyrapone (an inhibitor of cortisol synthesis) inhibited HT-induced masculinization of XX medaka. HT treatment caused elevation of whole-body levels of cortisol, while metyrapone suppressed the elevation by HT treatment during sexual differentiation. Moreover, cortisol and 33°C treatments inhibited female-type proliferation of germ cells as well as expression of follicle-stimulating hormone receptor (fshr) mRNA in XX medaka during sexual differentiation. These results strongly suggest that HT induces masculinization of XX medaka by elevation of cortisol level, which, in turn, causes suppression of germ cell proliferation and of fshr mRNA expression. Mol. Reprod. Dev. 77: 679,686, 2010. © 2010 Wiley-Liss, Inc. [source] Stage-dependent and alternative splicing of sGnRH messengers in rainbow trout testis during spermatogenesisMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2001Svetlana Uzbekova Abstract The gonadotropin releasing hormone (GnRH) has long been considered as a neuropeptide involved in the control of the reproductive cycle. However, the presence of GnRH and its receptors in various tissues, including ovary and testis, suggests a role as autocrine/paracrine factor. In the present study, we report the expression of the sGnRH-1 and sGnRH-2 genes encoding salmon GnRH in rainbow trout testis throughout testicular development and spermatogenesis. We demonstrate that both sGnRH mRNA are expressed prior of sexual differentiation. In adult, northern blot analysis indicates that sGnRH-2 transcripts are expressed in the testis at higher levels than sGnRH-1 messengers. Moreover, we observed that the expression of sGnRH-2, and not sGnRH-1, messengers was stage-dependent. sGnRH-2 mRNA expression decreases at the onset and progressively rebounds at the end of spermatogenesis. In addition, we demonstrate that a complex stage-dependent and differential splicing of the sGnRH-2 messengers occurs throughout spermatogenesis. We isolated five transcripts corresponding to sGnRH-2 messengers. Two of them may encode a novel and shortened GnRH-associated peptide containing 18 residues instead of 46. Our data provide new insight in the putative role of GnRH and GAP peptides as autocrine/paracrine factors of spermatogenesis. Mol. Reprod. Dev. 59:1,10, 2001. © 2001 Wiley-Liss, Inc. [source] Chloroplast signalling in the light induction of nuclear HSP70 genes requires the accumulation of chlorophyll precursors and their accessibility to cytoplasm/nucleusTHE PLANT JOURNAL, Issue 4 2000Janette Kropat Summary Chlorophyll precursors Mg-protoporphyrin IX and its monomethylester are candidates for plastid-derived molecules involved in light signalling from the chloroplast to the nucleus. The pool sizes of these two Mg2+ -containing porphyrins and of protoporphyrin IX transiently increased upon a shift of Chlamydomonas cultures from dark to light. This increase coincided with the accumulation of mRNAs encoded by the nuclear genes HSP70A and HSP70B. Analysis of a mutant (brs-1), previously shown to be defective in the light induction of these genes, revealed high levels of protoporphyrin IX but no light-induced increase in the levels of Mg2+ -containing porphyrins. Inhibitors of cytoplasmic protein synthesis prevented both the light-induced rise in pool levels and induction of the HSP70 genes. Similarly, pre-gametes, intermediates of sexual differentiation, lacked both responses to light. The block in light induction of the HSP70 genes in inhibitor-treated cells and in pre-gametes could be circumvented by the exogenous addition of Mg-protoporphyrin IX in the dark. This suggests an essential role for light-induced Mg-protoporphyrin IX accumulation in this chloroplast-to-nucleus signalling pathway. However, accumulation of this porphyrin in the dark , presumably in the chloroplast , did not result in induction. A second crucial role for light in this signalling pathway is postulated which makes this plastidic compound accessible to the cytoplasm/nucleus where the downstream signalling pathway may be activated. [source] | ||||||||||||||||||||||||||||