Proceedings of the National Academy of Sciences of the United States of AmericaJul 21, 2026

Single-cell map of the mouse ovary shows molecular changes linked to aging during the transition to reduced fertility

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Updated Jul 22, 2026

Abstract

Reproductive aging in mice leads to estropause, characterized by irregular estrous cycles and eventual cessation.

Irregularly cycling ovaries during the estropausal transition exhibited accelerated aging features compared to regularly cycling ovaries.
Cellular senescence markers increased in the ovaries, including heightened expression of the marker Cdkn1a.
Alterations in hormone regulation were observed in granulosa cells during the transition to estropause.
Increased transcriptional noise and changes in key aging pathways such as oxidative phosphorylation and proteostasis were noted.
This research provides a detailed atlas of cellular and molecular changes associated with ovarian aging and senescence.

Simplified

Reproductive aging in mice leads to estropause, characterized by estrous cycle irregularity and eventual cessation, yet its underlying mechanism remains unclear. Here, we present a comprehensive single-cell atlas of mouse ovaries across precisely defined reproductive stages-from young (regular cycling) through the estropausal transition (regular vs. irregular cycling) to post-estropause (acyclic)-and of ovary-specific senescent cells defined by high senescence-associated β-galactosidase activity. We mapped transcriptomic dynamics of ovarian aging and characterized the molecular features of ovarian senescent cells. Our analyses revealed that during the estropausal transition, irregularly cycling ovaries exhibited accelerated aging and cellular senescence features compared with regularly cycling counterparts, including increased transcriptional noise, altered conserved aging pathways such as oxidative phosphorylation and proteostasis, hormone dysregulation in granulosa cells, and elevated expression of the senescence marker Cdkn1a and senescence-associated secretory phenotype factors. This atlas delineates the cellular and molecular hallmarks of mouse ovarian aging and ovary-specific senescent cells, providing a resource for understanding the mechanisms underlying the estropausal transition.

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PubMed

Single-cell map of the mouse ovary shows molecular changes linked to aging during the transition to reduced fertility

Abstract

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