Human foetal ovary shares meiotic preventing factors with the developing testis

Frydman, Nelly; Poulain, Marine; Arkoun, Brahim; Duquenne, Clotilde; Tourpin, Sophie; Messiaen, Sébastien; Habert, René; Rouiller-Fabre, Virginie; Benachi, Alexandra; Livera, Gabriel

doi:10.1093/humrep/dew343

Cited by 17 publications

(28 citation statements)

References 46 publications

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“…However, in other organisms, including humans, Cyp26b1 expression is not downregulated during meiosis (Frydman et al, 2017). Cyp26b1 has a central role in suppressing meiosis in embryonic testes in mice, and is not expressed in developing ovaries during meiotic initiation.…”

Section: Future Directionsmentioning

confidence: 97%

“…Cyp26b1 has a central role in suppressing meiosis in embryonic testes in mice, and is not expressed in developing ovaries during meiotic initiation. However, in other organisms, including humans, Cyp26b1 expression is not downregulated during meiosis (Frydman et al, 2017). A recent comparative study with marsupials concludes that the roles of RA and Stra8 are conserved in the initiation of meiosis across Therian mammals while that of Cyp26b1 is not (Hickford et al, 2017).…”

Section: Future Directionsmentioning

confidence: 99%

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Retinoic acid signaling in regulation of meiosis during embryonic development in mice

Yadu

Kumar

2019

Genesis

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Summary In the embryonic gonads of mice, the genetic and epigenetic regulatory programs for germ cell sex specification and meiosis induction or suppression are intertwined. The quest for garnering comprehensive understanding of these programs has led to the emergence of retinoic acid (RA) as an important extrinsic factor, which regulates initiation of meiosis in female fetal germ cells that have attained a permissive epigenetic ground state. In contrast, germ cells in fetal testis are protected from the exposure to RA due to the activity of CYP26B1, an RA metabolizing enzyme, which is highly expressed in fetal testis. In this review, we provide an overview of the molecular mechanisms operating in fetal gonads of mice, which enable regulation of meiosis via RA signaling.

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Section: Future Directionsmentioning

confidence: 97%

Section: Future Directionsmentioning

confidence: 99%

Retinoic acid signaling in regulation of meiosis during embryonic development in mice

Yadu

Kumar

2019

Genesis

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“…However, in the fetal testis, Cyp26b1 degrades RA and prevents the expression of RA‐associated genes including Stra8 , resulting to no entry into meiosis (Bowles et al, ; Koubova et al, ; Kumar et al, ; Li, MacLean, Cameron, Clagett‐Dame, & Petkovich, ; MacLean, Li, Metzger, Chambon, & Petkovich, ). In support of this proposed mechanism, it has been found that in the human fetal ovary, two main meiosis‐preventing factors, Cyp26b1 and FGF9, are expressed in some germ cells and cause Stra8 repression and escape from meiosis (Frydman et al, ).…”

Section: Introductionmentioning

confidence: 93%

Meiotic initiation in chicken germ cells is regulated by Cyp26b1 and mesonephros

et al. 2019

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Our knowledge of mechanisms involved in the meiosis of chicken germ cells is very limited. In mammalian fetal ovaries, the onset of meiosis is dependent on retinoic acid and subsequent upregulation of the Stra8 gene. To clarify the mechanism of meiotic initiation in chicken germ cells, we investigated the role of Cyp26b1, a retinoic acid‐degrading enzyme. The Cyp26b1‐inhibitor, ketoconazole was used to treat the ex vivo‐cultured stage 36 gonads/mesonephroi. Then, the progression of meiosis was studied by histological and immunohistochemical analysis and the level of the transcript for Stra8 was evaluated by a quantitative reverse transcription‐polymerase chain reaction in individual ketoconazole‐treated gonads after 6 days in culture. The results revealed that meiosis was induced in both testes and right ovary upon inhibition of Cyp26b1 in the ex vivo‐cultured gonads, despite downregulation of Stra8 messenger RNA in the treated gonads. Also, meiosis was observed only when mesonephros was cultured alongside the left ovary. These findings demonstrate that in chicken, Stra8 is not the only factor for the entrance into meiosis, and Cyp26b1 and mesonephros play critical regulatory roles for the sex‐specific timing of meiotic initiation in birds.

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“…In human fetal testes, the mechanisms responsible for preventing meiosis are not completely understood (reviewed in Jørgensen & Rajpert-De Meyts 2014). However, several studies have found that CYP26B1 is expressed in both human fetal ovaries and testes, suggesting that, in contrast to mice, this is not a malespecific meiosis inhibitor (Childs et al 2011, Jørgensen et al 2012, Frydman et al 2017. Conversely, the roles of other meiosis-inhibiting factors e.g.…”

Section: Fetal Testis Developmentmentioning

confidence: 99%

Role of Nodal signalling in testis development and initiation of testicular cancer

Poulsen

Jørgensen

2019

Reproduction

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Testicular development from the initially bipotential gonad is a tightly regulated process involving a complex signalling cascade to ensure proper sequential expression of signalling factors and secretion of steroid hormones. Initially, Sertoli cell specification facilitates differentiation of the steroidogenic fetal Leydig cells and establishment of the somatic niche, which is critical in supporting the germ cell population. Impairment of the somatic niche during fetal life may lead to development of male reproductive disorders, including arrest of gonocyte differentiation, which is considered the first step in the testicular cancer pathogenesis. In this review, we will outline the signalling pathways involved in fetal testis development focusing on the Nodal pathway, which has recently been implicated in several aspects of testicular differentiation in both mouse and human studies. Nodal signalling plays important roles in germ cell development, including regulation of pluripotency factor expression, proliferation and survival. Moreover, the Nodal pathway is involved in establishment of the somatic niche, including formation of seminiferous cords, steroidogenesis and Sertoli cell function. In our outline of fetal testis development, important differences between human and mouse models will be highlighted to emphasise that information obtained from mouse studies cannot always be directly translated to humans. Finally, the implications of dysregulated Nodal signalling in development of the testicular cancer precursor, germ cell neoplasia in situ, and testicular dysgenesis will be discussed – none of which arise in rodents, emphasising the importance of human models in the effort to increase our understanding of origin and early development of these disorders.

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Human foetal ovary shares meiotic preventing factors with the developing testis

Abstract: This research was supported by the Université Paris Diderot-Paris 7 and Université Paris-Sud, CEA, INSERM, and Agence de la Biomédecine. The authors declare no conflict of interest.

Cited by 17 publications

References 46 publications

Retinoic acid signaling in regulation of meiosis during embryonic development in mice

Retinoic acid signaling in regulation of meiosis during embryonic development in mice

Meiotic initiation in chicken germ cells is regulated by Cyp26b1 and mesonephros

Role of Nodal signalling in testis development and initiation of testicular cancer

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