Single-Cell Transcriptomics Reveals Ovarian Aging and Senescent Cell Accumulation underlying the Estropausal Transition in Mice

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 versus 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.