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 underp...

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Bibliographic Details
Published in:Nature communications 2022-08, Vol.13 (1), p.4510-4510, Article 4510
Main Authors: Hu, Mengwen, Yeh, Yu-Han, Munakata, Yasuhisa, Abe, Hironori, Sakashita, Akihiko, Maezawa, So, Vidal, Miguel, Koseki, Haruhiko, Hunter, Neil, Schultz, Richard M., Namekawa, Satoshi H.
Format: Article
Language:English
Subjects:
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631/136/2434/1706
631/208/176/2016
631/337/100/2285
631/80/641/1633
Animals
Cell Cycle Proteins - metabolism
Chromatin
Chromatin - genetics
Demethylation
Deoxyribonucleic acid
Depletion
DNA
Epigenetics
Female
Females
Follicles
Gametocytes
Gene expression
Gene Silencing
Humanities and Social Sciences
Humans
Life span
Meiosis
Meiosis - genetics
Mice
multidisciplinary
Oocytes
Ovarian Reserve - genetics
Ovaries
Polycomb group proteins
Polycomb Repressive Complex 1 - metabolism
Programming
Prophase
Reproductive status
Science
Science (multidisciplinary)
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Summary: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. In humans, the ovarian reserve is maintained over decades by meiotic arrest of oocytes. Here the authors show that Polycomb Repressive Complex 1 (PRC1)-mediated epigenetic programming is essential for formation of ovarian reserve and thus female reproductive lifespan.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-31759-6