Department of Microbiology and Molecular Genetics, University of California, Davis, Davis, CA, USA.
Division of Reproductive Sciences, Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Nat Commun. 2022 Aug 10;13(1):4510. doi: 10.1038/s41467-022-31759-6.
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.
卵巢储备定义了女性的生殖寿命，在人类中，由于原始卵泡中减数分裂停滞的卵母细胞的稳健维持，生殖寿命可以跨越数十年。包括 DNA 去甲基化在内的表观遗传重编程伴随着减数分裂的进入，但支持卵巢储备生成和维持的染色质变化还未被很好地定义。我们报告称，多梳抑制复合物 1（PRC1）在围产期的小鼠卵母细胞中建立了抑制性染色质状态，该状态直接抑制了减数分裂前期-I 的基因表达程序，从而使卵母细胞向二价体阻滞转变。PRC1 功能障碍会导致卵巢储备耗尽，进而导致卵巢早衰。我们的研究证明了 PRC1 介导的基因沉默在女性生殖寿命中的基本作用，并揭示了建立卵巢储备所需的关键表观遗传编程窗口。
