Comparative analysis of human and mouse ovaries across age

The mouse is a tractable model for human ovarian biology, however its utility is limited by incomplete understanding of how transcription and signaling differ interspecifically and with age. We compared ovaries between species using three-dimensional imaging, single-cell transcriptomics, and functional studies. In mice, we mapped declining follicle numbers and oocyte competence during aging; in human ovaries, we identified cortical follicle pockets and decreases in density. Oocytes had species-specific gene expression patterns during growth that converged toward maturity. Age-related transcriptional changes were greater in oocytes than granulosa cells across species, although mature oocytes change more in humans. We identified ovarian sympathetic nerves and glia; axon density increased in aged ovaries and, when ablated in mice, perturbed folliculogenesis. This comparative atlas defines shared and species-specific hallmarks of ovarian biology.