Retinoic acid synthesis by ALDH1A proteins is dispensable for meiosis initiation in the mouse fetal ovary.

Abstract

In mammals, the timing of meiosis entry is regulated by signals from the gonadal environment. All-<i>trans</i> retinoic acid (ATRA) signaling is considered the key pathway that promotes <i>Stra8</i> (<i>stimulated by retinoic acid 8</i>) 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. <i>Aldh1a1</i> and <i>Aldh1a2,</i> 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 <i>Aldh1a1;Aldh1a2;Aldh1a3</i>, we show that <i>Stra8</i> 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.