Process Of Sexual Differentiation Research Articles

Dynamic and differential expression of the gonadal aromatase during the process of sexual differentiation in a novel transgenic cyp19a1a-eGFP zebrafish line

In zebrafish, there exists a clear need for new tools to study sex differentiation dynamic and its perturbation by endocrine disrupting chemicals. In this context, we developed and characterized a novel transgenic zebrafish line expressing green fluorescent protein (GFP) under the control of the zebrafish cyp19a1a (gonadal aromatase) promoter. In most gonochoristic fish species including zebrafish, cyp19a1a, the enzyme responsible for the synthesis of estrogens, has been shown to play a critical role in the processes of reproduction and sexual differentiation. This novel cyp19a1a-eGFP transgenic line allowed a deeper characterization of expression and localization of cyp19a1a gene in zebrafish gonads both at the adult stage and during development. At the adult stage, GFP expression was higher in ovaries than in testis. We showed a perfect co-expression of GFP and endogenous Cyp19a1a protein in gonads that was mainly localized in the cytoplasm of peri-follicular cells in the ovary and of Leydig and germ cells in the testis. During development, GFP was expressed in all immature gonads of 20 dpf-old zebrafish. Then, GFP expression increased in early differentiated female at 30 and 35dpf to reach a high GFP intensity in well-differentiated ovaries at 40dpf. On the contrary, males consistently displayed low GFP expression as compared to female whatever their stage of development, resulting in a clear dimorphic expression between both sexes. Interestingly, fish that undergoes ovary-to-testis transition (35 and 40dpf) presented GFP levels similar to males or intermediate between females and males. In this transgenic line our results confirm that cyp19a1a is expressed early during development, before the histological differentiation of the gonads, and that the down-regulation of cyp19a1a expression is likely responsible for the testicular differentiation. Moreover, we show that although cyp19a1a expression exhibits a clear dimorphic expression pattern in gonads during sexual differentiation, its expression persists whatever the sex suggesting that estradiol synthesis is important for gonadal development of both sexes. Monitoring the expression of GFP in control and exposed-fish will help determine the sensitivity of this transgenic line to EDCs and to refine mechanistic based-assays for the study of EDCs. In fine, this transgenic zebrafish line will be a useful tool to study physiological processes such as reproduction and sexual differentiation, and their perturbations by EDCs.

Developmental changes and day-night expression of the gonadotropin-inhibitory hormone system in the European sea bass: Effects of rearing temperature

The role of rearing temperature on fish development, sex differentiation and puberty has been largely addressed, but the impact of water temperature on the ontogeny of the main neuroendocrine systems controlling reproduction has received little attention. Gonadotropin-inhibitory hormone (GnIH) has been shown to act on gonadotropin-releasing hormone (GnRH) neurons and on the pituitary to inhibit gonadotropin release and synthesis in vertebrates, including sea bass, Dicentrarchus labrax. In the present study we investigated the effects of rearing temperature during the thermosensitive period (5–60days post-fertilization, dpf) on the expression of the GnIH gene (gnih) and its receptor (gnihr). Animals were maintained under two different conditions, low temperature (LT, 15°C) or high temperature (HT, 21°C), throughout the thermosensitive period and sampled from 5 to 360dpf at mid-light (ML) and mid-dark (MD). Our results showed significant effects of temperature on gnih and gnihr expression during the thermosensitive period, with higher transcript levels under LT condition. Some differences were also evident after the completion of the sex differentiation process. Moreover, we revealed daily variations in the developmental expression of gnih and gnihr, with higher diurnal mRNA levels at early stages (until 25dpf), and a shift to higher nocturnal expression levels at 300–360dpf, which corresponded with the beginning of the winter (reproductive season). To the best of our knowledge, this work represents the first study reporting the effects of rearing temperature on the transcription of gnih system genes, as well as its daily variations during the development of a fish species.

Appropriate rearing density in domesticated zebrafish to avoid masculinization: links with the stress response.

The zebrafish (Danio rerio) has become a well-established experimental model in many research fields but the loss of the primary sex-determining region during the process of domestication renders laboratory strains of zebrafish susceptible to the effects of environmental factors on sex ratios. Further, an essential husbandry aspect - the optimal rearing density to avoid stress-induced masculinization - is not known. We carried out two experiments: the first focusing on the effects of density on survival, growth and sex ratio by rearing zebrafish at different initial densities (9, 19, 37 and 74 fish per litre) for 3months (6-90 days post-fertilization, dpf), and the second focusing on the effects of cortisol during the sex differentiation period (15-45 dpf) for zebrafish reared at low density. The results showed an increase in the number of males in groups subjected to the two highest initial rearing densities; we also observed a reduction of survival and growth in a density-dependent manner. Furthermore, zebrafish treated with cortisol during the sex differentiation period showed a complete masculinization of the population; treatment with the cortisol synthesis inhibitor metyrapone negated the effects of exogenous cortisol. Our results indicate that the process of sex differentiation in domesticated zebrafish can be perturbed by elevated stocking density and that this effect is likely to be mediated by an increase in cortisol through the stress response. However, the underlying mechanism needs further study.

Temperature Preference and Sex Differentiation in African Catfish, Clarias gariepinus.

The African catfish Clarias gariepinus has a genetic sex determination system in which high temperature induces masculinization. The thermosensitive period for sex differentiation is short and occurs very early (from 6 to 8 days posthatching [dph]). As young juveniles can encounter high masculinizing temperature (36.5°C) in African water points, we aimed to determine the thermal preference of sexually undifferentiated juveniles and investigate if they spontaneously move toward high masculinizing temperature. Experiments were carried out in an environmental continuum (28-28-28°C and 28-32-36.5°C) made up of three 50-L aquariums connected together. Four hundred larvae from 10 different full-sib progenies were reared successively from 2 to 14 dph in these facilities. Before and after thermal treatments, fish were reared at 28°C until sex ratio determination at 70 dph. In the control continuum, fish were nearly equally distributed in the three compartments. Conversely, in the thermal continuum, compartment occupation significantly differed with progeny and period. During the highly thermosensitive period, two of five progenies significantly preferred (54.7% and 39.8% occupation) the 36.5°C compartment. All tested progenies reared in thermal continuum and separated 36.5°C aquarium showed a skewed sex ratio toward the male phenotype (78-100%). Nevertheless, no correlation was found between 36.5°C compartment occupation and sex ratio in thermal continuum groups. As masculinization temperature could be encountered in African water points during the spawning season, we discussed the adaptive advantage for the African catfish to display a sex differentiation process controlled by a temperature effect.

Floral Development of MonoeciousPseuduvaria Trimera(Annonaceae) and Comparative Morphology and Structure of Its Stamens and Indehiscent Staminodes

Premise of research. The comparative development of staminate and pistillate flowers in Pseuduvaria trimera (Annonaceae) was investigated for the first time to understand its sexual differentiation and developmental processes. The morphological and anatomical features of mature stamens and staminodes were also compared to clarify anther dehiscence and to understand the mechanism underlying staminode sterility.Methodology. Flowers at different developmental stages as well as mature stamens and staminodes were examined using SEM and LM.Pivotal results. Similar to other Annonaceae, the flowers of Pseuduvaria trimera have a complex whorled phyllotaxis. They have double positions in the outermost whorl of reproductive organs and variable numbers of stamens and carpels per whorl. The stomium region of each theca is composed of the septum and the stomium. The septum and stomium cells of stamens degenerate and facilitate anther opening, whereas those of staminodes remain intact and form indehiscent anthers.Conclu...

Transcriptome Sequencing Analysis and Functional Identification of Sex Differentiation Genes from the Mosquito Parasitic Nematode, Romanomermis wuchangensis.

Mosquito-transmitted diseases like malaria and dengue fever are global problem and an estimated 50–100 million of dengue or dengue hemorrhagic fever cases are reported worldwide every year. The mermithid nematode Romanomermis wuchangensis has been successfully used as an ecosystem-friendly biocontrol agent for mosquito prevention in laboratory studies. However, this nematode can not undergo sex differentiation in vitro culture, which has seriously affected their application of biocontrol in the field. In this study, based on transcriptome sequencing analysis of R. wuchangensis, Rwucmab-3, Rwuclaf-1 and Rwuctra-2 were cloned and used to investigate molecular regulatory function of sex differentiation. qRT-PCR results demonstrated that the expression level of Rwucmab-3 between male and female displayed obvious difference on the 3rd day of parasitic stage, which was earlier than Rwuclaf-1 and Rwuctra-2, highlighting sex differentiation process may start on the 3rd day of parasitic stage. Besides, FITC was used as a marker to test dsRNA uptake efficiency of R. wuchangensis, which fluorescence intensity increased with FITC concentration after 16 h incubation, indicating this nematode can successfully ingest soaking solution via its cuticle. RNAi results revealed the sex ratio of R. wuchangensis from RNAi treated groups soaked in dsRNA of Rwucmab-3 was significantly higher than gfp dsRNA treated groups and control groups, highlighting RNAi of Rwumab-3 may hinder the development of male nematodes. These results suggest that Rwucmab-3 mainly involves in the initiation of sex differentiation and the development of male sexual dimorphism. Rwuclaf-1 and Rwuctra-2 may play vital role in nematode reproductive and developmental system. In conclusion, transcript sequences presented in this study could provide more bioinformatics resources for future studies on gene cloning and other molecular regulatory mechanism in R. wuchangensis. Moreover, identification and functional analysis of sex differentiation genes may clarify the sex differentiation mechanism of R. wuchangensis, which are helpful to solve the uncompleted sex differentiation problem in vitro culture and the potential large-scale field application controlling the larvae of C. quinquefasciatus, A. aegypti and A. albopictus.

Recalled and current gender role behavior, gender identity and sexual orientation in adults with Disorders/Differences of Sex Development

The magnitude of sex differences in human brain and behavior and the respective contributions of biology versus socialization remain a topic of ongoing study in science. The preponderance of evidence attests to the notion that sexual differentiation processes are at least partially hormonally mediated, with high levels of prenatal androgens facilitating male-typed and inhibiting female-typed behaviors. In individuals with Disorders/Differences of Sex Development (DSD), hormonal profiles or sensitivities have been altered due to genetic influences, presumably affecting gender(ed) activity interests as well as gender identity development in a minority of the affected population. While continued postnatal androgen exposure in a number of DSD syndromes has been associated with higher rates of gender dysphoria and gender change, the role of a number of mediating and moderating factors, such as initial gender assignment, syndrome severity and clinical management remains largely unclear. Limited investigations of the associations between these identified influences and gendered development outcomes impede optimization of clinical care. Participants with DSD (n=123), recruited in the context of a Dutch multi-center follow-up audit, were divided in subgroups reflecting prenatal androgen exposure, genital appearance at birth and gender of rearing. Recalled childhood play and playmate preferences, gender identity and sexual orientation were measured with questionnaires and semi-structured interviews. Data were compared to those of control male (n=46) and female participants (n=79). The findings support that (a) prenatal androgen exposure has large effects on (gendered) activity interests, but to a much lesser extent on sexual orientation and that (b) initial gender of rearing remains a better predictor of gender identity contentedness than prenatal androgen exposure, beyond syndrome severity and medical treatment influences. Nonetheless, 3.3% of individuals with DSD in our sample self-reported gender dysphoria from an early age and changed gender, which further underlines the need for thorough long- term follow-up and specific clinical support.

No escape from mother's will: effects of maternal testosterone on offspring reproductive behaviour far into adulthood

In many animal species, mothers expose their embryos to maternal hormones. This provides a powerful pathway for affecting offspring phenotype and a potential mechanism for adaptive nongenomic inheritance. This has been studied extensively in birds because the embryo develops outside the mother's body, facilitating experimental studies. Some studies have demonstrated that maternal yolk testosterone (T) can have long-lasting effects into the period after fledging. However, these results are based on offspring in the juvenile stage or their first breeding season only. The lack of data further into adulthood limits a better assessment of the fitness consequences of prenatal T. In a series of previous experiments in the rock pigeon, Columba livia, we manipulated yolk T levels using oil-injected eggs as controls. In the present study, we examined the reproductive behaviour of birds from these eggs when they were 1–3 years old and housed together in a large aviary. Our results showed that males from T-injected eggs were less aggressive and females from T-injected eggs laid lighter eggs than controls. Moreover, the experimental birds showed strongly disassortative mating with respect to hormone treatment. There were no indications of treatment effects on the process of sexual differentiation. Our results indicate that the effects of prenatal T do not diminish over age and may last far into adulthood, which should be taken into account in assessing the fitness consequences of maternal hormones. They may also stimulate new physiological and neurobiological studies on the mechanisms underlying such long-lasting effects of prenatal T exposure.

First characterization and validation of turbot microRNAs

MicroRNAs (miRNAs) are highly conserved short non-coding RNAs which play a key role in a wide array of processes. They are usually at the center of regulatory networks modulating the expression of a large number of mRNAs. miRNAs have been found to regulate processes related to relevant aquaculture traits like growth or immune response; hence characterizing and studying the miRNA repertoire in farmed species is interesting for aquaculture purposes. Turbot (Scophthalmus maximus) is a commercially important flatfish characterized by adult bilateral asymmetry after larvae undergo metamorphosis during early development. Diverse turbot tissues from different developmental stages were pooled and sequenced for small RNA identification. A total of 306 turbot mature miRNAs, 299 known and 7 not previously described, were identified, placed on the turbot genome, and their precursor sequences predicted. Among them, 15 miRNAs involved in growth, immunity or sex differentiation processes and three novel microRNAs were technically validated along turbot early development (5, 15, 25, 35days post fertilization), encompassing endogenous to exogenous feeding transition and metamorphosis. Most of the selected miRNAs showed expression changes among tested stages. Then, putative mRNAs targets for these 18 miRNAs were identified by screening the turbot transcriptome using two different predictive algorithms. In summary, this is the first description of the turbot miRNA repertoire, which will be useful for future studies aiming to improve turbot aquaculture production, but also it represents a contribution to understand teleost miRNAs function. Statement of relevanceMicroRNAs are usually found in the center of regulatory networks, hence their characterization and study are critical for understanding a broad array of biological processes. The findings reported here – miRNA sequencing, characterization, mapping to the genome, validation of relevant and novel miRNAs and target prediction are an important resource for aquaculture, since understanding the involvement in immunology, growth or sex differentiation of these microRNAs can increase the knowledge on the physiology of these processes, which is important to better manipulate these traits and improve aquaculture production.

The Bromodomain testis-specific gene (Brdt) characterization and expression in gilthead seabream, Sparus aurata, and European seabass, Dicentrarchus labrax.

Multiple genes and transcription factors are involved in regulation and control of the complex process of sex determination and differentiation of fish species. Also more, several hormonal factors and some environmental conditions can also be adequate spawning strategies and stimuli for inducing reproduction of fish species. Brdt gene belongs to the bromodomain-extraterminal domain (BET) family of transcriptional coregulators. In mammals, Brdt gene is almost exclusively expressed in testis. Furthermore, Brdt protein is involved in elongating spermatids, and is required for proper spermatogenesis and male fertility. However, from our understanding of fish species, the role of this gene as key, during gametogenesis, still remains unknown. In this study, two Brdt mRNA transcripts were isolated from two teleostean fish species, gilt-head seabream and European seabass. In both species the shorter form lacked a functional C-terminal domain, which may involve a different function as transcriptional regulator. The pattern of Brdt expression showed that the highest levels occurred in the gonads. Significantly lower levels of expression were detected in brain, pituitary and different organ systems (heart, kidney, gills, among other somatic tissues) from both studied species. In situ hybridization approach evidenced that Brdt mRNA expression was restricted to specific cell-types of the germ line, during both oogenesis and spermatogenesis processes.

The study of the transformer gene from Bactrocera dorsalis and B. correcta with putative core promoter regions.

BackgroundThe transformer (tra) is a sex determining switch in different orders of insects, including Diptera, as in the family Tephritidae. The lifelong autoregulatory loop of tra female-specific splicing can be reset by the intervention of male-specific primary signals (M factor). In early development, the functional female and truncated male TRA proteins relay the sexual fates to the alternative splicing of a bisexual switch gene, doublesex (dsx) cascading the sexual differentiation processes. Bactrocera dorsalis (Hendel) and Bactrocera correcta (Bezzi) are among the Bactrocera model worldwide key pests. Area-wide integrated pest management using the male-only Sterile Insect Technique (SIT) relying on genetic sexing systems is effective in control programs. We undertook the molecular characterization and comparative studies of the tra orthologues in the Bactrocera species, including the Salaya1 genetic sexing strain (GSS).ResultsRT-PCR revealed that B. dorsalis tra (Bdtra) and B. correcta tra (Bctra) transcripts contained conservation of both constitutive exons and male-specific exons as in other Bactrocera. However, new Bdtra male-specific exons were retained, diversifying the pattern of the male-specifically spliced transcripts. The coding sequences of tra were highly conserved in Bactrocera (86–95 %) but less so among related genera (61–65 %) within the same Tephritidae family. A conservation of deduced amino acid sequences (18 residues), called the TEP region, was identified to be distinctive among tephritids. The 5’ regulatory sequence containing many structural characteristics of the putative core promoter was discovered in B. correcta. The expression patterns of Bdtra and Bctra were sex-specifically spliced and the signals relayed to the dsx genes in the adult wild-types. However, the coexistence of male- and female-specifically spliced transcripts (980 and 626 bp, respectively) of the B. dorsalis wild-type strain was found in the Salaya1 GSS adult males. The Bdtra RNA interference masculinized the XX karyotype females into pseudomales, but their testes were mostly not well developed.ConclusionsBdtra and Bctra have sex-specific splicing, similar to Bactroceras, Ceratitis capitata (Wiedemann), and Anastrephas. A newly identified TEP region is proposed in tephritids. A putative core promoter has been discovered in Bctra.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-016-0342-0) contains supplementary material, which is available to authorized users.

Thermosensitivity of the sex differentiation process in the African catfish, Clarias gariepinus: Determination of the thermosensitive period

Gonadal sex differentiation in gonochoristic fish is generally labile and under the control of two interacting processes: genetic sex determination (GSD) and environmental sex determination (ESD). Numerous experimental studies deal with temperature induced-sex differentiation in teleosts, but none focused on the African catfish Clarias gariepinus. The aim of this study was to confirm the thermosensitivity of the sex differentiation process and to determine the thermosensitive period during the African catfish development. Fish were exposed to high temperature (36°C) for 3days at different periods during ontogenesis. The treatment was applied every 3days from fertilization until 29dayspost-hatching (dph). Before and after the thermal treatment, fish were reared at 28°C. Gonadal development was histologically characterized on fish sampled at 10, 15, 20, 25, 35, 45, 55 and 70dph. Our results demonstrated that the African catfish displays a thermosensitivity of the sex differentiation process, with a masculinizing effect of high temperature (36°C). The most thermosensitive period extended from 6 to 8dph. Fish batches exposed to 36°C during this period showed a sex-ratio skewed towards the male phenotype, ranging from 58 to 100% (high inter-familial variability). The African catfish gonads (male and female) stayed histologically undifferentiated until 20dph. Obvious signs of gonadal differentiation clearly appeared at 25dph in females and at 45dph in males.Variability in sex-ratios between progenies and in the response to thermal treatment suggests a role of minor genetic factors and interactions between genomic and environmental determinants in the expression of the sexual phenotype. Statement of relevance1.This paper provides novel methods to control African catfish Clarias gariepinus sex differentiation through high temperature exposure and then to produce all-male populations.2.Our work underlines the possibility to significantly reduce high temperature (masculinizing effect) treatment period to 3days and consequently increase survival rate of progenies after treatment.3.This study also shows the inter-family variability of thermosensitivity on the sex differentiation process in Clarias gariepinus.

The Battle of the Sexes: Human Sex Development and Its Disorders.

The process of sexual differentiation is central for reproduction of almost all metazoan and therefore for maintenance of practically all multicellular organisms. In sex development we can distinguish two different processes: First, sex determination is the developmental decision that directs the undifferentiated embryo into a sexually dimorphic individual. In mammals, sex determination equals gonadal development. The second process known as sex differentiation takes place once the sex determination decision has been made through factors produced by the gonads that determine the development of the phenotypic sex. Most of the knowledge on the factors involved in sexual development came from animal models and from studies of cases in whom the genetic or the gonadal sex does not match the phenotypical sex, i.e., patients affected by disorders of sex development (DSD). Generally speaking, factors influencing sex determination are transcriptional regulators, whereas factors important for sex differentiation are secreted hormones and their receptors. This review focuses on the factors involved in gonadal determination, and whenever possible, references on the "prismatic" clinical cases are given.

북방전복 Haliotis discus hannai의 형태학적 성분화

This study was conducted to provide the reproductive biological information and basic data on the artificial sex control of Haliotis discus hannai. The morphological sex differentiation process of H. discus hannai could be classified into following five phases: 1) formation of gonad outer membrane (FGOM) (), 2) primordial germ cells (PGCs) appearance in the connective tissue between intestine and hepatopancreas (PAC), and formation of gonadal cavity (FGC) (SL ), 3) PGCs appearance in the epithelial layer of gonadal cavity (PAG) (SL ), 4) formation of gametogenic follicle and appearance of early oocytes and spermatogonia (FGOC) (SL ), 5) morphological sex differentiation (MSD) (). From histological analysis sex differentiation rate in SL 24.1-25.0 mm of H. discus hannai was 90.0% and sex ratio (female : male) was 1:0.8.

Comprehensive transcriptomic analysis of the process of gonadal sex differentiation in the turbot (Scophthalmus maximus)

The turbot is a flatfish with a ZW/ZZ sex determination system but with a still unknown sex determining gene(s), and with a marked sexual growth dimorphism in favor of females. To better understand sexual development in turbot we sampled young turbot encompassing the whole process of gonadal differentiation and conducted a comprehensive transcriptomic study on its sex differentiation using a validated custom oligomicroarray. Also, the expression profiles of 18 canonical reproduction-related genes were studied along gonad development. The expression levels of gonadal aromatase cyp19a1a alone at three months of age allowed the accurate and early identification of sex before the first signs of histological differentiation. A total of 56 differentially expressed genes (DEG) that had not previously been related to sex differentiation in fish were identified within the first three months of age, of which 44 were associated with ovarian differentiation (e.g., cd98, gpd1 and cry2), and 12 with testicular differentiation (e.g., ace, capn8 and nxph1). To identify putative sex determining genes, ∼4.000 DEG in juvenile gonads were mapped and their positions compared with that of previously identified sex- and growth-related quantitative trait loci (QTL). Although no genes mapped to the previously identified sex-related QTLs, two genes (foxl2 and 17βhsd) of the canonical reproduction-related genes mapped to growth-QTLs in linkage group (LG) 15 and LG6, respectively, suggesting that these genes are related to the growth dimorphism in this species.

Identification of the molecular sex‐differentiation period in the siberian sturgeon

Sexual development prior to gonadal sex differentiation is regulated by various molecular mechanisms. In fish, a "molecular sex-differentiation period" has been identified in species for which sex can be ascertained prior to gonadal sex differentiation. The present study was designed to identify such a period in a species for which no genetic sex markers or monosex populations are available. Siberian sturgeons undergo a slow sex-differentiation process over several months, so gonad morphology and gene expression was tracked in fish from ages 3-27 months to identify the sex-differentiation period. The genes amh, sox9, and dmrt1 were selected as male gonad markers; cyp19a1a and foxl2a as female gonad markers; and cyp17a1 and ar as markers of steroid synthesis and steroid receptivity. Sex differentiation occurred at 8 months, and was preceded by a molecular sex-differentiation period at 3-4 months, at which time all of the genes except ar showed clear expression peaks. amh and sox9 expression seemed to be involved in male sexual development whereas dmrt1, a gene involved in testis development in metazoans, unexpectedly showed a pattern similar to those of the genes known to be involved in female gonadal sex differentiation (cyp19a1 and foxl2a). In conclusion, the timing of and gene candidates involved with molecular sex differentiation in the Siberian sturgeon were identified.

Prenatal Exposures of Male Rats to the Environmental Chemicals Bisphenol A and Di(2-Ethylhexyl) Phthalate Impact the Sexual Differentiation Process.

The increasing incidence of reproductive anomalies, described as testicular dysgenesis syndrome, is thought to be related to the exposure of the population to chemicals in the environment. Bisphenol A (BPA) and di(2-ethylhexyl)phthalate (DEHP), which have hormonal and antihormonal activity, have attracted public attention due to their presence in consumer products. The present study investigated the effects of BPA and DEHP on reproductive development. Timed-pregnant female rats were exposed to BPA and DEHP by gavage from gestational days 12 to 21. Results showed that prenatal exposures to test chemicals exerted variable effects on steroidogenic factor 1 and GATA binding protein 4 protein expression and increased (P < .05) sex-determining region Y-box 9 and antimüllerian hormone protein in the infantile rat testis compared with levels in the control unexposed animals. Pituitary LHβ and FSHβ subunit protein expression was increased (P < .05) in BPA- and DEHP-exposed prepubertal male rats but were decreased (P < .05) in adult animals relative to control. Exposure to both BPA and DEHP in utero inhibited (P < .05) global DNA hydroxymethylation in the adult testis in association with altered DNA methyltransferase protein expression. Together the present data suggest that altered developmental programming in the testes associated with chemical exposures are related to the disruption of sexual differentiation events and DNA methylation patterns. The chemical-induced effects impact the development of steroidogenic capacity in the adult testis.

Lasting effects of early exposure to temperature on the gonadal transcriptome at the time of sex differentiation in the European sea bass, a fish with mixed genetic and environmental sex determination.

BackgroundSex in fish is plastic and in several species can be influenced by environmental factors. In sensitive species, elevated temperatures have a masculinizing effect. Previous studies on the effects of temperature on gene expression have been restricted to a few cognate genes, mostly related to testis or ovarian development, and analyzed in gonads once they had completed the process of sex differentiation. However, studies on the effect of temperature at the whole gonadal transcriptomic level are scarce in fish and, in addition, temperature effects at the time of sex differentiation at the transcriptomic level are also unknown. Here, we used the European sea bass, a gonochoristic teleost with a polygenic sex determination system influenced by temperature, and exposed larvae to elevated temperature during the period of early gonad formation. Transcriptomic analysis of the gonads was carried out about three months after the end of temperature exposure, shortly after the beginning of the process of sex differentiation.ResultsElevated temperature doubled the number of males with respect to untreated controls. Transcriptomic analysis of early differentiating female gonads showed how heat caused: 1) an up-regulation of genes related to cholesterol transport (star), the stress response (nr3c1) and testis differentiation (amh, dmrt, etc.), 2) a decrease in the expression of genes related to ovarian differentiation such as cyp19a1a, and 3) an increase in the expression of several genes related to epigenetic regulatory mechanisms (hdac11, dicer1, ehmt2, jarid2a, pcgf2, suz12, mettl22).ConclusionsTaken together, the results of this study contribute to the understanding of how the early environment sets permanent changes that result in long-lasting consequences, in this case in the sexual phenotype. Results also show the usefulness of comparing the effects of heat on the behavior of cognate genes related to sex differentiation as well as that of genes involved in establishing and maintaining cell identity through epigenetic mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1862-0) contains supplementary material, which is available to authorized users.

Intrauterine sexual differentiation: biosyntesis and action of sexual steroid hormones

The objective of this review was to describe sexual differentiation events in mammals, relating them to biosynthesis of sexual steroid hormones and their mechanisms of action. Cholesterol is the precursor of sexual steroid hormone biosynthesis via action of several enzymes converting these hormones. Progestagens hormones serve as substrate for the production of androgens, which in turn serve as substrate for estrogen hormones. These hormones are responsible for sexual differentiation and reproductive cycles of mammals. Sexual differentiation process comprises determining the sexual chromosomes XX or XY + SRY and other genes linked to them, differentiation of gonads in testis or ovary, differentiation of internal and external male or female genital organs from undifferentiated anatomical structures present in the embryo, which is dependent on the presence or absence of testes and the production of anti-Mullerian hormone and testosterone; and secondary sexual differentiation, which is the response of various tissues to hormones produced by the gonads, interacting with genes linked to sexual chromosomes to increase or decrease the differences in sexual phenotype. However, some differences between the sexes and some anomalies of sexual differentiation are not explained only by these sexual hormonal effects, but also by the effect of genes encoded in sexual chromosomes.

Gender development and sexuality in disorders of sex development.

Understanding psychological development in individuals with disorders of sex development (DSD) is important for optimizing their clinical care and for identifying paths to competence and health in all individuals. In this paper, we focus on psychological outcomes likely to be influenced by processes of physical sexual differentiation that may be atypical in DSD, particularly characteristics related to being male or female (those that show sex differences in the general population, gender identity, and sexuality). We review evidence suggesting that (a) early androgens facilitate several aspects of male-typed behavior, with large effects on activity interests, and moderate effects on some social and personal behaviors (including sexual orientation) and spatial ability; (b) gender dysphoria and gender change occur more frequently in individuals with DSD than in the general population, with rates varying in relation to syndrome, initial gender assignment, and medical treatment; and (c) sexual behavior may be affected by DSD through several paths related to the condition and treatment, including reduced fertility, physical problems associated with genital ambiguity, social stigmatization, and hormonal variations. We also consider limitations to current work and challenges to studying gender and sexuality in DSD. We conclude with suggestions for a research agenda and a proposed research framework.