Meiosis occurs normally in the fetal ovary of mice lacking all retinoic acid receptors

Nadège Vernet , Diana Condrea , Chloé Mayere , Betty Féret , Muriel Klopfenstein , William Magnant , Violaine Alunni , Marius Telentin , Sirine Souali-Crespo , Serge Nef , Manuel Mark , Norbert B Ghyselinck (1)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire

Gametes are generated through a specialized cell differentiation process, meiosis, which, in ovaries of most mammals , is initiated during fetal life. All-trans retinoic acid (ATRA) is considered as the molecular signal triggering meiosis initiation. In the present study, we analyzed female fetuses ubiquitously lacking all ATRA nuclear receptors (RAR), obtained through a tamoxifen-inducible cre recombinase-mediated gene targeting approach. Unexpectedly , mutant oocytes robustly expressed meiotic genes, including the meiotic gatekeeper STRA8. In addition, ovaries from mutant fetuses grafted into adult recipient females yielded offspring bearing null alleles for all Rar genes. Thus, our results show that RAR are fully dispensable for meiotic initiation, as well as for the production of functional oocytes. Assuming that the effects of ATRA all rely on RAR, our study goes against the current model according to which meiosis is triggered by endogenous ATRA in the developing ovary. It therefore revives the search for the meiosis-inducing substance.

Domaines: Sciences du Vivant [q-bio]

Nadège Vernet, Diana Condrea, Chloé Mayere, Betty Féret, Muriel Klopfenstein, et al.. Meiosis occurs normally in the fetal ovary of mice lacking all retinoic acid receptors. Science Advances , 2020, 6, pp.eaaz1139. ⟨10.1126/sciadv.aaz1139⟩. ⟨hal-02988715⟩