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 in 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.
Authors
- Faranak Fattahi (ORCID: https://orcid.org/0000-0002-9473-8596)
- Angela M. Detweiler (ORCID: https://orcid.org/0000-0001-7026-5467)
- Tara I. McIntyre (ORCID: https://orcid.org/0000-0001-6670-9977)
- James M. Gardner (ORCID: https://orcid.org/0000-0003-3470-9520)
- Leah C. Dorman (ORCID: https://orcid.org/0000-0002-5511-887X)
- Michael Borja (ORCID: https://orcid.org/0009-0006-4527-3370)
- Norma Neff (ORCID: https://orcid.org/0000-0001-7141-5420)
- Mariko H. Foecke (ORCID: https://orcid.org/0000-0002-9205-940X)
- Eliza A. Gaylord (ORCID: https://orcid.org/0000-0003-2986-4630)
- Diana J. Laird (ORCID: https://orcid.org/0000-0002-4930-0560)
- Bikem Soygur (ORCID: https://orcid.org/0000-0002-2749-9871)
- Ryan M. Samuel (ORCID: https://orcid.org/0000-0002-9473-1378)
- Juan Du (ORCID: https://orcid.org/0000-0003-4701-3573)
- Ritwicq Arjyal
- Amy Laird (ORCID: https://orcid.org/0000-0002-7592-9901)
Institutions
- Portland State University (US)
- Buck Institute for Research on Aging (US)
- Oregon Health & Science University (US)
- University of California, San Francisco (US)
- Reproductive Science Center (US)
- Chan Zuckerberg Initiative (United States) (US)
- Broad Center (US)
Publication Details
- Journal
- Science
- Published
- 2025-10-09
- DOI
- https://doi.org/10.1126/science.adx0659
- Citations
- 11
- Primary Topic
- Reproductive Biology and Fertility
- Type
- article
- Field-Weighted Citation Impact
- 20.66