Overview
Isola et al. (Nature Aging, 2024) profiled mouse ovaries at 3 and 9 months by scRNA-seq (n=4/group, ~14,000 cells, 15 clusters) to capture changes before fertility loss.
- Immune expansion. Immune cells more than doubled, driven by Type 1 NKT and Type 17 γδ T cells. Confirmed by flow cytometry.
- Fibrosis mechanism. Collagen deposition rose, but fibroblast collagen expression didn't — Mmp2 and the collagenase pathway were downregulated. Fibrosis reflects impaired degradation.
- Theca as profibrotic driver. Theca cells upregulated TGFB1/TGFB2/SMAD3. TGFβ signaling shifted from broad to immune-restricted with age.
- Follicular stress. Granulosa cells induced proinflammatory (IFNG, TNF) and fibrogenic pathways; oocytes showed mitochondrial dysfunction; AMH signaling broke down.
- Senescence priming. Vascular endothelium showed TP53/CDKN1A/CDKN2A upstream activity without overt senescence transcripts.