Asynchronous female reproductive organ ageing as revealed by single-cell transcriptomic atlas

Successful pregnancies require fine coordination among the reproductive organs. Reproductive research has focused on ovarian ageing, the uterus and oviduct have received much less attention; whether these organs age synchronously with the ovaries remains unclear. Here, we established a single-cell transcriptomic atlas of the ovary, oviduct, and uterus across the murine reproductive lifespan. Organ–organ communication patterns were identified using cell-specific hormone receptor analysis. The ageing hallmarks (including DNA damage, cellular senescence, and apoptosis, etc.) were evaluated for each cell type. Analysis of these ageing-related gene set scores combined with changes in morphology and molecular signatures revealed that the ovary aged earlier and faster than the oviduct and uterus; this was also confirmed in human reproductive tissues. Our single-cell transcriptomic atlas provides molecular insights into reproductive ageing and its asynchronization for the reproductive organs across the murine reproductive lifespan, which may reveal the causes of declining fertility at advanced ages. We performed scRNA-seq analyses of the ovary, oviduct, and uterus across the female reproductive lifespan of Mus musculus [C57BL/6 mice, 5 days (5D), 5 weeks (5W), 3 months (3M), 6 months (6M), 9 months (9M), 12 months (12M), and 15 months (15M)].