Sci Adv. 2020 May 22;6(21):eaaz1261. doi: 10.1126/sciadv.aaz1261. eCollection 2020 May.
Anne-Amandine Chassot1, Morgane Le Rolle1, Geneviève Jolivet2, Isabelle Stevant3, Jean-Marie Guigonis4,5, Fabio Da Silva1,6, Serge Nef3, Eric Pailhoux2, Andreas Schedl1, Norbert B Ghyselinck7, Marie-Christine Chaboissier1
1 Université Côte d’Azur, CNRS, Inserm, iBV, Nice, France.
2 Université Paris-Saclay, INRAE, ENVA, BREED, 78350, Jouy-en-Josas, France.
3 Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
4 Université Côte d’Azur, UMR E4320, CEA, F-06107 Nice, France.
5 Plateforme “Bernard Rossi”, Faculté de Médecine, Université Côte d’Azur, F-06107 Nice, France.
6 Division of Molecular Embryology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
7 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Génétique Fonctionnelle et Cancer, CNRS UMR7104, Inserm U1258, Université de Strasbourg (UNISTRA), 1 rue Laurent Fries, F-67404 Illkirch CEDEX, France.
In mammals, the timing of meiosis entry is regulated by signals from the gonadal environment. All-trans retinoic acid (ATRA) signaling is considered the key pathway that promotes Stra8 (stimulated by retinoic acid 8) expression and, in turn, meiosis entry. This model, however, is debated because it is based on analyzing the effects of exogenous ATRA on ex vivo gonadal cultures, which not accurately reflects the role of endogenous ATRA. Aldh1a1 and Aldh1a2, two retinaldehyde dehydrogenases synthesizing ATRA, are expressed in the mouse ovaries when meiosis initiates. Contrary to the present view, here, we demonstrate that ATRA-responsive cells are scarce in the ovary. Using three distinct gene deletion models for Aldh1a1;Aldh1a2;Aldh1a3, we show that Stra8 expression is independent of ATRA production by ALDH1A proteins and that germ cells progress through meiosis. Together, these data demonstrate that ATRA signaling is dispensable for instructing meiosis initiation in female germ cells.