Anti-Müllerian hormone and freemartinism : inhibition of germ cell development and induction of seminiferous cord-like structures in rat fetal ovaries exposed in vitro to purified bovine AMH

Vigier, B.; Watrin, Françoise; Magre, Solange; Tran, Daniel; Garrigou, O.; Forest, Maguelone G.; Josso, Nathalie

doi:10.1051/rnd:19880709

Cited by 24 publications

(16 citation statements)

References 26 publications

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“…Indeed, TAM fails to induce any MD regression if injected into female embryos (Salzgeber et al 1981), when such a regression would be expected from our results. However, TAM-treated females exhibit slightly masculinized ovaries (Salzgeber et al 1981) supporting the idea that TAM actually allows the AMH produced by the ovary to be released (Stoll et al 1980;Vigier et al 1987Vigier et al , 1988.…”

Section: Discussionmentioning

confidence: 89%

Action of estradiol and tamoxifen on the M�llero-regressive activity of the chick embryonic testis assayed in vivo by organotypic grafting

et al. 1993

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In the chick, the implantation of a testis graft from a 13-day-old male donor embryo into the extra-embryonic coelom of 3-day-old female embryos induces the total regression of their Müllerian ducts because of the anti-Müllerian hormone (AMH or MIS) secreted by the implant. Pre-treatment of the donors with estradiol (E2), between day 12 and day 13, counteracts in a significant way the Müllero-regressive activity of the implant. Co-treatment of donors at the same stage with both Tamoxifen (TAM) and E2 restores the initially observed activity, thus demonstrating the presence of Tamoxifen-sensitive estrogen receptors at the late stage of treatment in the Sertoli cells responsible for AMH secretion. The treatment of 3-day-old male donor embryos with E2 causes the differentiation of their left gonad into an ovotestis which provides implants totally devoid of Müllero-regressive activity. The additional treatment with TAM of the grafted host embryos, does not modify the results obtained when E2-treated male gonads are grafted to host embryos not treated with TAM. This shows that the lack of Müllero-regressive activity exhibited by the E2-treated male gonads does not depend on the estrogens they may secrete during the time of the assay, i.e., it cannot be attributed to a protecting action of estrogens on the MDs of the host. Our results therefore favor the idea that E2 down-regulates AMH. The relevance of such a regulation to the phenomenon of Müllerian duct maintenance, either in the E2-feminized male or in the female chick embryo, is discussed.

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Section: Discussionmentioning

confidence: 89%

Action of estradiol and tamoxifen on the M�llero-regressive activity of the chick embryonic testis assayed in vivo by organotypic grafting

et al. 1993

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“…Serum concentrations of AMH are similar in freemartins and their male twins, suggesting that AMH may mediate the disruption of ovarian development (Vigier et al, 1984). This idea is supported by the finding that recombinant AMH can induce a freemartin effect in fetal rat ovaries in culture, resulting in depletion of germ cells and formation of testis cordlike structures (Vigier et al, 1988). We have further investigated the effects of AMH on the development of XX gonads in culture to better understand how AMH induces this freemartin effect and to identify potential roles of AMH during normal testis development.…”

Section: Introductionmentioning

confidence: 80%

AMH induces mesonephric cell migration in XX gonads

Ross

Tilman

Yao

et al. 2003

Molecular and Cellular Endocrinology

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Migration of mesonephric cells into XY gonads is a critical early event in testis cord formation. Based on the fact that anti-Müllerian hormone (AMH) can induce testis cord formation in XX gonads, we investigated whether AMH plays a role in the induction of cell migration. Addition of recombinant AMH induced mesonephric migration into XX gonads in culture. AMH-treated XX gonads displayed increased vascular development and altered morphology of the coelomic epithelium, both features of normal testis differentiation. AMH did not induce markers of Sertoli or Leydig cell differentiation. We examined early testis development in Amh-deficient mice, but found no abnormalities, suggesting that any function AMH may have in vivo is redundant. Other transforming growth factor (TGF-β) family proteins, bone morphogenetic proteins (BMP2 and BMP4) show similar inductive effects on XX gonads in culture. Although neither BMP2 nor BMP4 is expressed in embryonic XY gonads, our findings suggest that a TGF-β signalling pathway endogenous to the XY gonad may be involved in regulation of mesonephric cell migration. The factors involved in this process remain to be identified.

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“…As its expression is switched off at the time when meiosis first occurs in the testis, it is thought that AMH may interfere with germ cells entering and completing meiosis [Münsterberg and Lovell-Badge, 1991]. Vigier et al [1988] showed that bovine AMH will induce a 'freemartin' effect in E13 and E14 rat ovaries in vitro, mimicking the effect of attachment of a bovine female fetus to a male twin by chorionic vascular anastomoses in utero. In this natural condition, the Müllerian ducts of the female regress under the effect of AMH from the male testis; growth of the freemartin ovary is arrested, germ cells cease multiplication and seminiferous cord-like structures develop.…”

Section: Discussionmentioning

confidence: 99%

“…Work in our laboratory has previously shown that when ovaries of E13 mice are cultured for 4 days in testis-conditioned medium (generated by culture of E13 testes for 2 days), the number of oocytes present is approximately half that of contralateral ovaries cultured in control medium [Tavendale et al, 1992], though this occurred without any inhibition of Müllerian duct development. When bovine AMH is added to cultures of rat fetal ovaries, a higher concentration of AMH is required to reduce the germ cell number than to cause Müllerian duct regression [Vigier et al, 1988]. Therefore, the testicular secreted factor affecting ovarian germ cell survival in vitro may not be AMH alone.…”

Section: Discussionmentioning

confidence: 99%

Developing Mouse Sertoli Cells in vitro: Effects on Developing Ovaries in Co-Culture and Production of Anti-Müllerian Hormone

Mackay¹,

Willerton²,

Ballingall³

et al. 2004

Cells Tissues Organs

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Previous work in our laboratory showed that pre-Sertoli cells adopt an epithelial phenotype when cultured in the presence of reconstituted basement membrane (RBM), and so cultures were established with and without this substrate. Biological activity of isolated developing mouse Sertoli cells maintained in vitro was assessed in the current study by utilising a co-culture approach, to determine whether the cells were capable of affecting ovarian differentiation. Developing Sertoli cells isolated at embryonic day (E) 12.5 exerted a deleterious effect on E12.5 ovaries in co-culture, inducing a loss of germ cells. However, when cells were isolated a day later and co-cultured with E13.5 ovaries (after entry to meiosis has begun), germ cells survived and showed evidence of meiosis, although ovigerous cords in co-cultures were masculinised compared to those of control cultured ovaries. Thus, both stages examined showed biological effects; cultured pre-Sertoli cells explanted at E12.5 showed a negative effect on female germ cells, whereas those explanted at E13.5 masculinised ovigerous cords. The functional status of isolated developing mouse Sertoli cells in vitro was further assessed by immunocytochemistry to investigate the expression of anti-Müllerian hormone, an early product of pre-Sertoli cells. Positive immunostaining was seen in developing Sertoli cells in vitro, particularly where cells had been explanted to an RBM substrate, demonstrating that good epithelial morphology is associated with improved function. Our culture system is therefore well suited for investigating factors produced by developing Sertoli cells, their role in influencing testicular morphogenesis and their potential to perturb ovarian differentiation. We believe that this in vitro approach provides a more physiological assessment compared with the knockout mouse model, where global effects of genes with housekeeping functions can compromise overall development.

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Anti-Müllerian hormone and freemartinism : inhibition of germ cell development and induction of seminiferous cord-like structures in rat fetal ovaries exposed in vitro to purified bovine AMH

Cited by 24 publications

References 26 publications

Action of estradiol and tamoxifen on the M�llero-regressive activity of the chick embryonic testis assayed in vivo by organotypic grafting

Action of estradiol and tamoxifen on the M�llero-regressive activity of the chick embryonic testis assayed in vivo by organotypic grafting

AMH induces mesonephric cell migration in XX gonads

Developing Mouse Sertoli Cells in vitro: Effects on Developing Ovaries in Co-Culture and Production of Anti-Müllerian Hormone

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