The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform

Margaret M Mccarthy - One of the best experts on this subject based on the ideXlab platform.

  • microglia are essential to Masculinization of brain and behavior
    The Journal of Neuroscience, 2013
    Co-Authors: Kathryn M Lenz, Bridget M. Nugent, Rachana Haliyur, Margaret M Mccarthy
    Abstract:

    Brain sexual differentiation in rodents results from the perinatal testicular androgen surge. In the preoptic area (POA), estradiol aromatized from testosterone upregulates the production of the proinflammatory molecule, prostaglandin E2 (PGE2) to produce sex-specific brain development. PGE2 produces a two-fold greater density of dendritic spines in males than in females and masculinizes adult copulatory behavior. One neonatal dose of PGE2 masculinizes the POA and behavior, and simultaneous treatment with an inhibitor of additional prostaglandin synthesis prevents this Masculinization, indicating a positive feedforward process that leads to sustained increases in PGE2. The mechanisms underlying this feedforward process were unknown. Microglia, the primary immunocompetent cells in the brain, are active neonatally, contribute to normal brain development, and both produce and respond to prostaglandins. We investigated whether there are sex differences in microglia in the POA and whether they influence developmental Masculinization. Neonatal males had twice as many ameboid microglia as females and a more activated morphological profile, and both estradiol and PGE2 masculinized microglial number and morphology in females. Microglial inhibition during the critical period for sexual differentiation prevented sex differences in microglia, estradiol-induced Masculinization of dendritic spine density, and adult copulatory behavior. Microglial inhibition also prevented the estradiol-induced upregulation of PGE2, indicating that microglia are essential to the feedforward process through which estradiol upregulates prostaglandin production. These studies demonstrate that immune cells in the brain interact with the nervous and endocrine systems during development, and are crucial for sexual differentiation of brain and behavior.

  • histone deacetylation during brain development is essential for permanent Masculinization of sexual behavior
    Endocrinology, 2011
    Co-Authors: Ken-ichi Matsuda, Margaret M Mccarthy, Bridget M. Nugent, Hiroko Mori, Donald W Pfaff, Mitsuhiro Kawata
    Abstract:

    Epigenetic histone modifications are emerging as important mechanisms for conveyance of and maintenance of effects of the hormonal milieu to the developing brain. We hypothesized that alteration of histone acetylation status early in development by sex steroid hormones is important for sexual differentiation of the brain. It was found that during the critical period for sexual differentiation, histones associated with promoters of essential genes in Masculinization of the brain (estrogen receptor α and aromatase) in the medial preoptic area, an area necessary for male sexual behavior, were differentially acetylated between the sexes. Consistent with these findings, binding of histone deacetylase (HDAC) 2 and 4 to the promoters was higher in males than in females. To examine the involvement of histone deacetylation on Masculinization of the brain at the behavioral level, we inhibited HDAC in vivo by intracerebroventricular infusion of the HDAC inhibitor trichostatin A or antisense oligodeoxynucleotide dire...

  • prostaglandin e2 induced Masculinization of brain and behavior requires protein kinase a ampa kainate and metabotropic glutamate receptor signaling
    The Journal of Neuroscience, 2009
    Co-Authors: Christopher L. Wright, Margaret M Mccarthy
    Abstract:

    Prostaglandin E2 (PGE2) mediates the Masculinization of adult sex behavior in rats in response to the surge in serum testosterone at approximately birth. Measures of behavioral Masculinization correlate with a twofold increase in spinophilin protein and the density of dendritic spines in the medial preoptic area (POA). Of the four receptors for PGE2, EP2 and EP4 are required for the Masculinization of behavior by PGE2. EP2 and EP4 couple to Gs-proteins, activating protein kinase A (PKA). By using H89 ( N -[2-( p -bromo-cinnamylamino)-ethyl]-5-isoquinoline-sulfon-amide 2HCl) and Ht31, disruptors of PKA signaling, we have determined that PKA signaling is required for the Masculinization of behavior by PGE2. Glutamatergic signaling often mediates PGE2 signaling; therefore, we tested whether inhibition of AMPA/kainate and metabotropic glutamate receptor (mGluR) signaling prevents PGE2-induced behavioral Masculinization and whether activation of glutamate receptors mimics PGE2. Females treated neonatally with NBQX (2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[ f ]quinoxaline) plus LY341495 [(2 S )-2-amino-2-[(1 S ,2 S )-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid] combined (AMPA/kainate and mGluR inhibitors, respectively) before PGE2 did not exhibit as many mounts or intromission-like behaviors or initiate these behaviors as quickly as animals treated with PGE2 alone. Animals neonatally treated with kainate, (±)-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD) (type I mGluR agonist), or the two combined mounted as frequently and initiated mounting behavior as quickly as those given PGE2. Ht31 does not prevent the Masculinization of behavior by ACPD plus kainate cotreatment; rather, the coadministration of NBQX plus LY341495 prevents the forskolin-induced formation of POA dendritic spine-like processes. We conclude that PKA, AMPA/kainate, and metabotropic glutamate receptor signaling are necessary for the effects of PGE2, that each receptor individually suffices to organize behavior, and that PKA is upstream of the glutamate receptors.

  • the role of neonatal nmda receptor activation in defeminization and Masculinization of sex behavior in the rat
    Hormones and Behavior, 2008
    Co-Authors: Jaclyn M Schwarz, Margaret M Mccarthy
    Abstract:

    Normal development of the male rat brain involves two distinct processes, Masculinization and defeminization, that occur during a critical period of brain sexual differentiation. Masculinization allows for the capacity to express male sex behavior in adulthood, and defeminization eliminates or suppresses the capacity to express female sex behavior in adulthood. Despite being separate processes, both Masculinization and defeminization are induced by neonatal estradiol exposure. Though the mechanisms underlying estradiol-mediated Masculinization of behavior during development have been identified, the mechanisms underlying defeminization are still unknown. We sought to determine whether neonatal activation of glutamate NMDA receptors is a necessary component of estradiol-induced defeminization of behavior. We report here that antagonizing glutamate receptors during the critical period of sexual differentiation blocks estradiol-induced defeminization but not Masculinization of behavior in adulthood. However, enhancing NMDA receptor activation during the same critical period mimics estradiol to permanently induce both defeminization and Masculinization of sexual behavior.

  • Masculinization induced by neonatal exposure to PGE2 or estradiol alters c-fos induction by estrous odors in adult rats
    Physiology & Behavior, 2008
    Co-Authors: Bridget M. Nugent, Christopher L. Wright, Margaret M Mccarthy
    Abstract:

    Abstract Processing of relevant olfactory and pheromonal cues has long been known as an important process necessary for social and sexual behavior in rodents. Several nuclei that receive input from the vomeronasal projection pathway are involved in sexual behavior and show changes in immediate early gene expression after stimulation with a variety of sex-related stimuli. The nuclei in this pathway are sexually dimorphic due to the early patterning events induced by estradiol derived from testicular androgens, which developmentally defeminize and masculinize the brain and adult sexual behavior. Masculinization can be induced independently of estradiol via prostaglandin-E 2 (PGE 2 ), and therefore assessed separately from defeminization. Here we examined the effects of brain defeminization and Masculinization on neuronal response to sex-related odors using Fos, the protein product of the immediate early gene c -fos , as an indicator of activity. Female rat pups treated with a cyclooxygenase-2 inhibitor, to reduce PGE 2 , plus estradiol, estradiol alone, and PGE 2 alone were exposed to estrous female odor as adults and the resulting Fos expression was examined in the medial amygdala, preoptic area, and ventromedial nucleus of the hypothalamus. Defeminized and/or masculinized females all showed patterns of Fos activity similar to control males and significantly different from control females. These results suggest that early exposure to estradiol and PGE 2 do not affect olfaction in females, but switch the activity pattern of sex-related nuclei in females to resemble that of males following exposure to sexually-relevant cues.

Gen Yamada - One of the best experts on this subject based on the ideXlab platform.

  • regulation of Masculinization androgen signalling for external genitalia development
    Nature Reviews Urology, 2018
    Co-Authors: Shoko Matsushita, Kentaro Suzuki, Yukiko Ogino, Alvin R Acebedo, Aki Murashima, Daiki Kajioka, Shinichi Miyagawa, Ryuma Haraguchi, Gen Yamada
    Abstract:

    The biology of Masculinization is fundamentally important for understanding the embryonic developmental processes that are involved in the development of the male reproductive tract, external genitalia, and also the tumorigenesis of prostate cancer. The molecular mechanisms of Masculinization are of interest to many researchers and clinicians involved in varied fields, including molecular developmental biology, cancer research, endocrinology, and urology. Androgen signalling is mediated by the nuclear androgen receptor, which has fundamental roles in Masculinization during development. Various modes of androgen signalling, including 5α-dihydrotestosterone-induced regulation of mesenchymal cell proliferation, have been observed in Masculinization. Such regulation is essential for regulating urogenital tissue development, including external genitalia development. Androgen-induced genes, such as MAFB, which belongs to the activator protein 1 (AP-1) superfamily of genes, have essential roles in male urethral formation, and disruption of its signalling can interfere with urethral formation, which often results in hypospadias. Another AP-1 superfamily gene, ATF3, could be responsible for some instances of hypospadias in humans. These androgen-dependent signals and downstream events are crucial for not only developmental processes but also processes of diseases such as hypospadias and prostate cancer.

  • androgen regulates mafb expression through its 3 utr during mouse urethral Masculinization
    Endocrinology, 2016
    Co-Authors: Shoko Matsushita, Kentaro Suzuki, Yukiko Ogino, Shinjiro Hino, Tetsuya Sato, Mikita Suyama, Takahiro Matsumoto, Akiko Omori, Satoshi Inoue, Gen Yamada
    Abstract:

    External genitalia are prominent organs showing hormone-dependent sexual differentiation. Androgen is an essential regulator of Masculinization of the genital tubercle, which is the anlage of external genitalia. We have previously shown that v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) is an androgen-inducible regulator of embryonic urethral Masculinization in mice. However, it remains unclear how androgen regulates Mafb expression. The current study suggests that the Mafb 3′ untranslated region (UTR) is an essential region for its regulation by androgen. We identified 2 functional androgen response elements (AREs) in Mafb 3′UTR. Androgen receptor is bound to such AREs in 3′UTR during urethral Masculinization. In addition to 3′UTR, Mafb 5′UTR also showed androgen responsiveness. Moreover, we also demonstrated that β-catenin, one of genital tubercle Masculinization factors, may be an additional regulator of Mafb expression during urethral Masculinization. This study provides insigh...

  • the Masculinization programming window
    Endocrine development, 2014
    Co-Authors: Michelle Welsh, Hiroko Suzuki, Gen Yamada
    Abstract:

    Sexual differentiation is a tightly regulated series of events which transform the indifferent gonads and genitalia into sex-specific structures. This is driven by hormones produced by the fetal testes, primarily testosterone (T). However, Masculinization of each structure does not occur synchronously and, until recently, it was presumed that androgens also control this Masculinization over a broad period of fetal life, coincident with the period of fetal T production. However, a common fetal Masculinization programming window (MPW) has been identified in male and female rodent models in which androgens must act to masculinize all components of the reproductive tract and allow their later complete development. Impaired androgen action only within this MPW can induce cryptorchidism and hypospadias. This MPW is likely to occur between 8-14 weeks' gestation in humans. Studies in transgenic mice have begun to investigate some of the underlying mechanisms involved. Anogenital distance is predictive of the incidence of disorders, such as azoospermia, hypospadias and cryptorchidism, and could provide a noninvasive, lifelong indicator of androgen action within this MPW, useful in clinical assessment of patients with disorders of sexual development. In addition, several diagnostic characteristics of the external genitalia are also useful in investigating this MPW.

  • the role of sonic hedgehog gli2 pathway in the Masculinization of external genitalia
    Endocrinology, 2011
    Co-Authors: Shinichi Miyagawa, Akiko Omori, Naomi Nakagata, Aki Murashima, Ryuma Haraguchi, Daisuke Matsumaru, Yoshihiko Satoh, Jun Motoyama, Taisen Iguchi, Gen Yamada
    Abstract:

    During embryogenesis, sexually dimorphic organogenesis is achieved by hormones produced in the gonad. The external genitalia develop from a single primordium, the genital tubercle, and their Masculinization processes depend on the androgen signaling. In addition to such hormonal signaling, the involvement of nongonadal and locally produced Masculinization factors has been unclear. To elucidate the mechanisms of the sexually dimorphic development of the external genitalia, series of conditional mutant mouse analyses were performed using several mutant alleles, particularly focusing on the role of hedgehog signaling pathway in this manuscript. We demonstrate that hedgehog pathway is indispensable for the establishment of male external genitalia characteristics. Sonic hedgehog is expressed in the urethral plate epithelium, and its signal is mediated through glioblastoma 2 (Gli2) in the mesenchyme. The expression level of the sexually dimorphic genes is decreased in the glioblastoma 2 mutant embryos, suggesting that hedgehog signal is likely to facilitate the Masculinization processes by affecting the androgen responsiveness. In addition, a conditional mutation of Sonic hedgehog at the sexual differentiation stage leads to abnormal male external genitalia development. The current study identified hedgehog signaling pathway as a key factor not only for initial development but also for sexually dimorphic development of the external genitalia in coordination with androgen signaling.

Richard M Sharpe - One of the best experts on this subject based on the ideXlab platform.

  • prostaglandins Masculinization and its disorders effects of fetal exposure of the rat to the cyclooxygenase inhibitor indomethacin
    PLOS ONE, 2013
    Co-Authors: Afshan Dean, William Mungall, Chris Mckinnell, Richard M Sharpe
    Abstract:

    Recent studies have established that Masculinization of the male reproductive tract is programmed by androgens in a critical fetal ‘Masculinization programming window’ (MPW). What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice implicated prostaglandin (PG)-mediation of androgen-induced Masculinization, but this has never been followed up. We therefore investigated if PGs might mediate androgen effects in the MPW by exposing pregnant rats to indomethacin (which blocks PG production by inhibiting cyclooxygenase activity) during this period and then examining if androgen production or action (Masculinization) was affected. Pregnant rats were treated with indomethacin (0.8 mg/kg/day; e15.5–e18.5) to encompass the MPW. Indomethacin exposure decreased fetal bodyweight (e21.5), testis weight (e21.5) and testicular PGE2 (e17.5, e21.5), but had no effect on intratesticular testosterone (ITT; e17.5) or anogenital index (AGI; e21.5). Postnatally, AGI, testis weight and blood testosterone were unaffected by indomethacin exposure and no cryptorchidism or hypospadias occurred. Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% (p<0.001) in adulthood, an effect that is unexplained. Our results demonstrate that indomethacin can effectively decrease intra-testicular PGE2 level. However, the resulting male phenotype does not support a role for PGs in mediating androgen-induced Masculinization during the MPW in rats. The contrast with previous mouse studies is unexplained but may reflect a species difference.

  • the effect of dihydrotestosterone exposure during or prior to the Masculinization programming window on reproductive development in male and female rats
    International Journal of Andrology, 2012
    Co-Authors: Afshan Dean, Lee B Smith, Sheila Macpherson, Richard M Sharpe
    Abstract:

    Summary Masculinization is programmed by androgen exposure during a Masculinization programming window (MPW). Deficiency in MPW androgen action results in reduced size of all reproductive organs and anogenital distance (AGD) and reproductive disorders. Although timing of MPW closing has been defined, what determines ‘opening’ and ‘closing’ of the MPW remains unknown. To test whether initiation of testosterone production ⁄ action defines the opening of the window, we first demonstrated that androgen receptor mRNA and protein are expressed prior to the MPW, and then investigated whether Masculinization could be advanced or enhanced by treating pregnant rats with either 1 or 10 mg ⁄ kg ⁄ day dihydrotestosterone (DHT) prior to (early window, EW; e11.5–e14.5) or during the MPW (e15.5–e18.5), and then evaluating offspring in foetal life (e18.5, e21.5), early puberty (day 25) or adulthood (day 75). DHT treatment did not affect pregnancy duration, birth, litter or pup size. DHT exposure in either time window did not advance foetal male development (Wolffian duct coiling) and had no effect on AGD, testis, penis and ventral prostate (VP) size at any age when measured; there was a tendency towards smaller penis size. In contrast, exposure of females to 10 mg DHT in either time window induced varying degrees of Masculinization, including stabilization of the Wolffian duct and increased AGD (e21.5, Pnd25), VP formation, more male-like phallus structure, absence of nipples and vaginal opening and, in some adult females, gross fluid distension of the uterus (hydrometrocolpos); these effects were generally more pronounced after exposure in the MPW than in the EW. In conclusion, exposure of the male rat foetus to additional androgens prior to or during the MPW does not advance or enhance any measured parameter of reproductive development. Therefore, androgen availability plays no role in determining timing of the MPW. Susceptibility of the female reproductive system to androgens may precede the MPW.

  • steroidogenesis in the fetal testis and its susceptibility to disruption by exogenous compounds
    Endocrine Reviews, 2009
    Co-Authors: Hayley M Scott, Ian J Mason, Richard M Sharpe
    Abstract:

    Masculinization depends on adequate production of testosterone by the fetal testis within a specific “Masculinization programming window.” Disorders resulting from subtle deficiencies in this process are common in humans, and environmental exposures/lifestyle could contribute causally because common therapeutic and environmental compounds can affect steroidogenesis. This evidence derives mainly from rodent studies, but because there are major species differences in regulation of steroidogenesis in the fetal testis, this may not always be a guide to potential effects in the human. In addition to direct study of the effects of compounds on steroidogenesis, information also derives from study of Masculinization disorders that result from mutations in genes in pathways regulating steroidogenesis. This review addresses this issue by critically reviewing the comparative timing of production and regulation of steroidogenesis in the fetal testis of humans and of rodents and its susceptibility to disruption; where...

  • identification in rats of a programming window for reproductive tract Masculinization disruption of which leads to hypospadias and cryptorchidism
    Journal of Clinical Investigation, 2008
    Co-Authors: Michelle Welsh, Hayley M Scott, Philippa T K Saunders, Mark Fisken, Gary R Hutchison, Lee B Smith, Richard M Sharpe
    Abstract:

    Becoming a phenotypic male is ultimately determined by androgen-induced Masculinization. Disorders of fetal Masculinization, resulting in hypospadias or cryptorchidism, are common, but their cause remains unclear. Together with the adult-onset disorders low sperm count and testicular cancer, they can constitute a testicular dysgenesis syndrome (TDS). Although Masculinization is well studied, no unifying concept explains normal male reproductive development and its abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or androgens and showed that Masculinization of all reproductive tract tissues was programmed by androgen action during a common fetal programming window. This preceded morphological differentiation, when androgen action was, surprisingly, unnecessary. Only within the programming window did blocking androgen action induce hypospadias and cryptorchidism and altered penile length in male rats, all of which correlated with anogenital distance (AGD). Androgen-driven Masculinization of females was also confined to the same programming window. This work has identified in rats a common programming window in which androgen action is essential for normal reproductive tract Masculinization and has highlighted that measuring AGD in neonatal humans could provide a noninvasive method to predict neonatal and adult reproductive disorders. Based on the timings in rats, we believe the programming window in humans is likely to be 8–14 weeks of gestation.

Takeshi Kitano - One of the best experts on this subject based on the ideXlab platform.

  • high temperature causes Masculinization of genetically female medaka by elevation of cortisol
    Molecular Reproduction and Development, 2010
    Co-Authors: Yuki Hayashi, Hiroshi Kobira, Toshiya Yamaguchi, Eri Shiraishi, Takashi Yazawa, Toshiaki Hirai, Yasuhiro Kamei, Takeshi Kitano
    Abstract:

    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.

  • tamoxifen induces Masculinization of genetic females and regulates p450 aromatase and mullerian inhibiting substance mrna expression in japanese flounder paralichthys olivaceus
    Molecular Reproduction and Development, 2007
    Co-Authors: Takeshi Kitano, Eri Shiraishi, Norifumi Yoshinaga, Takashi Koyanagi
    Abstract:

    Japanese flounder, Paralichthys olivaceus, provides an excellent model to elucidate the roles of sex steroid hormones in gonadal sex differentiation because the sex is easily altered by sex steroid treatments or water temperature control during the sex differentiation. We have previously shown that high water temperature, an aromatase inhibitor (fadrozole), or 17α-methyltestosterone treatment causes the sex-reversal from genetic females to phenotypic males and suppression of mRNA expression of ovary-type P450 aromatase (P450arom), which is a steroidogenic enzyme responsible for the conversion of androgens to estrogens, in Japanese flounder. In the present study, we demonstrate that treatment of the genetic females with anti-estrogen (tamoxifen) leads to their Masculinization, suppresses P450arom mRNA expression, and induces mRNA expression of Mullerian inhibiting substance (MIS), a member of the transforming growth factor-β (TGF-β) superfamily, while it has no effect on mRNAs expression of estrogen receptor-α (ERα) and ERβ. In contrast, 17β-estradiol counteracted Masculinization of the genetic females by tamoxifen or high water temperature treatment, up-regulated P450arom mRNA expression, and down-regulated MIS mRNA expression. These results strongly suggest that estrogen signaling through ERs dramatically influences the gonadal sex differentiation by regulating P450arom and MIS mRNA expression. Mol. Reprod. Dev. 74: 1171–1177, 2007. © 2007 Wiley-Liss, Inc.

  • tributyltin causes Masculinization in fish
    Environmental Toxicology and Chemistry, 2003
    Co-Authors: Yohei Shimasaki, Takeshi Kitano, Yuji Oshima, Suguru Inoue, Nobuyoshi Imada, Tsuneo Honjo
    Abstract:

    We examined the effect of tributyltin (TBT) on the sex differentiation process in genetically female Japanese flounder (Paralichthys olivaceus). The fish were fed an artificial diet containing tributyltin oxide (TBTO) at concentrations of 0.1 and 1.0 μg/g diet from 35 to 100 d after hatching, which includes the sex differentiation period. The ratio of sex-reversed males significantly increased to 25.7% of the flounder fed the 0.1 μg/g diet and to 31.1% of those fed the 1.0 μg/g diet compared with the control (2.2%). From morphological and histological examination of the fish in the TBT-treated groups, normal females had typical ovaries and sex-reversed males had typical testes. These results clearly demonstrated the Masculinization of flounder exposed to TBTO. This is the first report of TBT inducing sex reversal in vertebrates.

Yann Guiguen - One of the best experts on this subject based on the ideXlab platform.

  • high temperature increases the Masculinization rate of the all female xx rainbow trout mal population
    PLOS ONE, 2014
    Co-Authors: Karina Valdivia, Alexis Fostier, Elodie Jouanno, Jeannicolas Volff, Delphine Galianaarnoux, Rene Guyomard, Louise Helary, Brigitte Mourot, Edwige Quillet, Yann Guiguen
    Abstract:

    Salmonids are generally considered to have a robust genetic sex determination system with a simple male heterogamety (XX/XY). However, spontaneous Masculinization of XX females has been found in a rainbow trout population of gynogenetic doubled haploid individuals. The analysis of this Masculinization phenotype transmission supported the hypothesis of the involvement of a recessive mutation (termed mal). As temperature effect on sex differentiation has been reported in some salmonid species, in this study we investigated in detail the potential implication of temperature on Masculinization in this XX mal-carrying population. Seven families issued from XX mal-carrying parents were exposed from the time of hatching to different rearing water temperatures ((8, 12 and 18°C), and the resulting sex-ratios were confirmed by histological analysis of both gonads. Our results demonstrate that Masculinization rates are strongly increased (up to nearly two fold) at the highest temperature treatment (18°C). Interestingly, we also found clear differences between temperatures on the Masculinization of the left versus the right gonads with the right gonad consistently more often masculinized than the left one at lower temperatures (8 and 12°C). However, the Masculinization rate is also strongly dependent on the genetic background of the XX mal-carrying families. Thus, Masculinization in XX mal-carrying rainbow trout is potentially triggered by an interaction between the temperature treatment and a complex genetic background potentially involving some part of the genetic sex differentiation regulatory cascade along with some minor sex-influencing loci. These results indicate that despite its rather strict genetic sex determinism system, rainbow trout sex differentiation can be modulated by temperature, as described in many other fish species.

  • rainbow trout gonadal Masculinization induced by inhibition of estrogen synthesis is more physiological than Masculinization induced by androgen supplementation
    Biology of Reproduction, 2008
    Co-Authors: Denise Vizziano, Daniel Baron, Gwenaelle Randuineau, Sophie Mahe, Chantal Cauty, Yann Guiguen
    Abstract:

    The present study was designed to obtain new insights into fish gonadal sex differentiation by comparing the effects of two different masculinizing treatments on some candidate gene expression profiles. Masculinization was induced in rainbow trout, Oncorhynchus mykiss, genetic all-female populations using either an active fish androgen (11betaAnd, 11betahydroxyandrostenedione) or an aromatase inhibitor (ATD, 1,4,6-androstatriene-3,17-dione). The expression profiles of 100 candidate genes were obtained by real-time RT-PCR, and 46 profiles displayed a significant differential expression between control populations (males and females) and ATD/ 11betaAnd-treated populations. These expression profiles were grouped in four temporally correlated expression clusters. Among the common responses shared by the two masculinizing treatments, the inhibition of some early female differentiating genes (cyp19a1, foxl2a, fst, and fshb) appears to be crucial for effective Masculinization, suggesting that these genes act together via a short regulation loop to maintain high sex-specific ovarian expression of cyp19a1. This simultaneous down-regulation of female-specific genes could be triggered by some testicular genes, such as dmrt1, nr0b1 (also known as dax1), and pdgfra, which are quickly up-regulated by the two masculinizing treatments. In contrast to 11betaAnd, ATD quickly restored the expression levels of steroidogenesis related genes (cyp11b2.1, cyp11b2.2, hsd3b1, cyp17a, star, and nr5a1) and some Sertoli cell markers (sox9a2 and amh )t o the expression levels observed during control testicular differentiation. This demonstrates that these genes are probably not needed for active Masculinization and that the inhibition of endogenous estrogen synthesis produces a much more complete and specific testicular pattern of gene expression than that observed following androgen-induced Masculinization.