Expression of <i>Sox9</i> in granulosa cells lacking the estrogen receptors, ERα and ERβ

Dupont, Sonia; Dennefeld, Christine; Krust, Andrée; Chambon, Pierre; Mark, Manuel

doi:10.1002/dvdy.10202

Cited by 45 publications

(32 citation statements)

References 38 publications

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“…. Moreover, the coexistence of some granulosa cells with sexual bipotentiality in the first follicles is consistent with the ovotestis-like phenotype in various partial XX sex reversal models such as the Esr1/Esr2 (estrogen receptor a/b) (Couse et al, 1999;Dupont et al, 2003), Foxl2/Wnt4 (Schmidt et al, 2004;Uda et al, 2004;Ottolenghi et al, 2007) and Rspo1-null ovaries (Chassot et al, 2008). For example, in ovaries of Foxl2/Wnt4-double-null mice, it was reported that the testis-cord-like tubules in the medullary region harbored well-differentiated spermatogonia, in contrast to the ovarian structures including oocytes in the cortex region (Ottolenghi et al, 2007).…”

Section: Discussionsupporting

confidence: 78%

“…For example, in ovaries of Foxl2/Wnt4-double-null mice, it was reported that the testis-cord-like tubules in the medullary region harbored well-differentiated spermatogonia, in contrast to the ovarian structures including oocytes in the cortex region (Ottolenghi et al, 2007). In Esr1/Esr2-double-null prepubertal ovaries, it was also shown that the initial transdifferentiation into the seminiferous-like tubules with SOX9-positive Sertoli-like cells appears to be found in the first wave of folliculogenesis in the centro-medullary region (Dupont et al, 2003). The present data using a partial sex reversal model of the grafted ovaries also demonstrated that, in the wild-type ovarian transplants, spontaneous transdifferentiation of pre-granulosa cells into SOX9-positive Sertoli-like cells is repeatedly found in ovarian medullary region ( Fig.…”

Section: Discussionmentioning

confidence: 99%

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Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries

Harikae

Miura

Shinomura

et al. 2013

Journal of Cell Science

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SummaryIn mammalian sex determination, SRY directly upregulates the expression of SOX9, the master regulatory transcription factor in Sertoli cell differentiation, leading to testis formation. Without SRY action, the bipotential gonadal cells become pre-granulosa cells, which results in ovarian follicle development. When, where and how pre-granulosa cells are determined to differentiate into developing ovaries, however, remains unclear. By monitoring SRY-dependent SOX9 inducibility (SDSI) in an Sry-inducible mouse system, we were able to identify spatiotemporal changes in the sexual bipotentiality/plasticity of ovarian somatic cells throughout life. The early pre-granulosa cells maintain the SDSI until 11.5 d.p.c., after which most pre-granulosa cells rapidly lose this ability by 12.0 d.p.c. Unexpectedly, we found a subpopulation of the pre-granulosa cells near the mesonephric tissue that continuously retains SDSI throughout fetal and early postnatal stages. After birth, these SDSI-positive pre-granulosa cells contribute to the initial round of folliculogenesis by the secondary follicle stage. In experimental sex reversal of 13.5-d.p.c. ovaries grafted into adult male nude mice, the differentiated granulosa cells re-acquire the SDSI before other signs of masculinization. Our data provide direct evidence of an unexpectedly high sexual heterogeneity of granulosa cells in developing mouse ovaries in a stage-and region-specific manner. Discovery of such sexually bipotential granulosa cells provides a novel entry point to the understanding of masculinization in various cases of XX disorders of sexual development in mammalian ovaries.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries

Harikae

Miura

Shinomura

et al. 2013

Journal of Cell Science

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“…However, definitive evidence that oestrogens play a critical role in maintaining ovarian structure has been found recently. In XX genetic female mice with targeted disruption of the genes encoding oestrogen receptors and (ER KO mice) or aromatase (ArKO mice), Leydig cells differentiate from interstitial cells, and seminiferous tubule-like structures presenting Sertoli cells expressing SOX9 differentiate from pre-existing granulosa cells after birth (Couse et al 1999, Britt et al 2002, Dupont et al 2003. If ArKO female mice are fed a diet containing phyto-oestrogens, the appearance of Leydig and Sertoli cells is postponed and reduced.…”

Section: Discussionmentioning

confidence: 99%

Oestrogens and temperature-dependent sex determination in reptiles: all is in the gonads

Pieau¹,

Dorizzi²

2004

Journal of Endocrinology

156

117

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In many species of oviparous reptiles, the first steps of gonadal sex differentiation depend on the incubation temperature of the eggs. Feminization of gonads by exogenous oestrogens at a male-producing temperature and masculinization of gonads by antioestrogens and aromatase inhibitors at a female-producing temperature have irrefutably demonstrated the involvement of oestrogens in ovarian differentiation. Nevertheless, several studies performed on the entire gonad/adrenal/ mesonephros complex failed to find differences between male-and female-producing temperatures in oestrogen content, aromatase activity and aromatase gene expression during the thermosensitive period for sex determination. Thus, the key role of aromatase and oestrogens in the first steps of ovarian differentiation has been questioned, and extragonadal organs or tissues, such as adrenal, mesonephros, brain or yolk, were considered as possible targets of temperature and sources of the oestrogens acting on gonadal sex differentiation.In disagreement with this view, experiments and assays carried out on the gonads alone, i.e. separated from the adrenal/mesonephros, provide evidence that the gonads themselves respond to temperature shifts by modifying their sexual differentiation and are the site of aromatase activity and oestrogen synthesis during the thermosensitive period. Oestrogens act locally on both the cortical and the medullary part of the gonad to direct ovarian differentiation. We have concluded that there is no objective reason to search for the implication of other organs in the phenomenon of temperature-dependent sex determination in reptiles. From the comparison with data obtained in other vertebrates, we propose two main directions for future research: to examine how transcription of the aromatase gene is regulated and to identify molecular and cellular targets of oestrogens in gonads during sex differentiation, in species with strict genotypic sex determination and species with temperature-dependent sex determination.

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“…Moreover, Sox9 mRNA is increased in adult ovaries of mice lacking the presence of estrogen receptors (Couse et al 1999, Dupont et al 2003.…”

Section: Figurementioning

confidence: 99%

Changes in gonadal gene network by exogenous ligands in temperature-dependent sex determination

Matsumoto¹,

Yatsu²,

Taylor³

et al. 2013

Journal of Molecular Endocrinology

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We examined the expression of candidate sex-determining genes in the red-eared slider turtle (Trachemys scripta) during the temperature-sensitive period (TSP). Aromatase and Rspo1 were used as markers of ovarian differentiation and Sox9 was used as a marker of testicular differentiation. Eggs were incubated at a male-producing temperature (26 8C or MPT) and a female-producing temperature (31 8C or FPT). First, eggs at the beginning of the TSP (stage 16) were topically treated with the steroid hormones 17b-estradiol (E 2 ), testosterone in combination with aromatase inhibitor (AICT), the E 2 antagonist (ICI 182 780), and the androgen antagonist (flutamide). Secondly, gonads were removed at stage 16 and treated in vitro with E 2 , AICT, or hormone antagonists. At the FPT, AICT in ovo suppressed aromatase and Rspo1, while activating Sox9. At the MPT, E 2 treatment rapidly increased aromatase and Rspo1, while suppressing Sox9. Treatment with the E 2 antagonist in ovo decreased aromatase at the FPT. Treatment with the androgen antagonist in ovo increased aromatase and Rspo1 at early time points at MPT and decreased Sox9 at MPT at later developmental stages. Treatment of isolated gonads cultured in vitro with AICT at FPT decreased aromatase and Rspo1 and E 2 increased the expression of these genes at MPT. In vitro treatment with E 2 antagonist suppressed aromatase and Rspo1 expression at FPT. Overall, our results suggest that exogenous ligands dictate gonadal development by redirecting the expression of candidate sex-determining genes within the genetic cascades induced by temperature.

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Expression of Sox9 in granulosa cells lacking the estrogen receptors, ERα and ERβ

Cited by 45 publications

References 38 publications

Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries

Heterogeneity in sexual bipotentiality and plasticity of granulosa cells in developing mouse ovaries

Oestrogens and temperature-dependent sex determination in reptiles: all is in the gonads

Changes in gonadal gene network by exogenous ligands in temperature-dependent sex determination

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