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

Mengwen Hu, Yu-Han Yeh, Yasuhisa Munakata, Hironori Abe, Akihiko Sakashita, So Maezawa, Miguel Vidal, Haruhiko Koseki, Neil Hunter, Richard M. Schultz and Satoshi H. Namekawa ()
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Mengwen Hu: University of California, Davis
Yu-Han Yeh: University of California, Davis
Yasuhisa Munakata: University of California, Davis
Hironori Abe: University of California, Davis
Akihiko Sakashita: Perinatal Institute, Cincinnati Children’s Hospital Medical Center
So Maezawa: Perinatal Institute, Cincinnati Children’s Hospital Medical Center
Miguel Vidal: Centro de Investigaciones Biológicas Margarita Salas, Department of Cellular and Molecular Biology
Haruhiko Koseki: RIKEN Center for Allergy and Immunology
Neil Hunter: University of California, Davis
Richard M. Schultz: University of Pennsylvania
Satoshi H. Namekawa: University of California, Davis

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-31759-6

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