PRC1-mediated epigenetic programming is required to generate the ovarian reserve

The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve. Overall design: RNA-seq analysis using PRC1ctrl and PRC1cKO P1 or P5 non-growing oocytes; Cut&Run analysis using PRC1ctrl and PRC1cKO P1 non-growing oocytes or wildtype (stella-GFP) P1 non-growing oocytes