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Divergent roles of CYP26B1 and endogenous retinoic acid in mouse fetal gonads

Abstract : In female mammals, germ cells enter meiosis in the fetal ovaries, while in males, meiosis is prevented until postnatal development. Retinoic acid (RA) is considered the main inducer of meiotic entry, as it stimulates Stra8 which is required for the mitotic/meiotic switch. In fetal testes, the RA-degrading enzyme CYP26B1 prevents meiosis initiation. However, the role of endogenous RA in female meiosis entry has never been demonstrated in vivo. In this study, we demonstrate that some effects of RA in mouse fetal gonads are not recapitulated by the invalidation or up-regulation of CYP26B1. In organ culture of fetal testes, RA stimulates testosterone production and inhibits Sertoli cell proliferation. In the ovaries, short-term inhibition of RA-signaling does not decrease $Stra8$ expression. We develop a gain-of-function model to express CYP26A1 or CYP26B1. Only CYP26B1 fully prevents STRA8 induction in female germ cells, confirming its role as part of the meiotic prevention machinery. CYP26A1, a very potent RA degrading enzyme, does not impair the formation of STRA8-positive cells, but decreases Stra8 transcription. Collectively, our data reveal that CYP26B1 has other activities apart from metabolizing RA in fetal gonads and suggest a role of endogenous RA in amplifying Stra8, rather than being the initial inducer of $Stra8$. These findings should reactivate the quest to identify meiotic preventing or inducing substances.
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https://hal.archives-ouvertes.fr/hal-03625032
Contributor : Emilie TRAUTMANN Connect in order to contact the contributor
Submitted on : Friday, April 1, 2022 - 4:17:28 PM
Last modification on : Tuesday, June 14, 2022 - 10:42:00 AM

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Laura Bellutti, Emilie Abby, Sophie Tourpin, Sébastien Messiaen, Delphine Moison, et al.. Divergent roles of CYP26B1 and endogenous retinoic acid in mouse fetal gonads. Biomolecules, MDPI, 2019, 9 (10), pp.536. ⟨10.3390/biom9100536⟩. ⟨hal-03625032⟩

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