biostudies-literatureIsola JVVGlobal Consortium for Reproductive Longevity and Equality - GCRLE-4501NIA NIH HHSU.S. Department of Health & Human Services | NIH | National Institute on AgingODCDC CDC HHSGlobal Consortium for Reproductive Longevity and Equality - GCRLE-0523U.S. Department of Health & Human Services | NIH | NIH Office of the DirectorPresbyterian Health FoundationNIH HHS145-162https://www.ebi.ac.uk/biostudies/studies/S-EPMC10798902biostudies-literatureUnknown4(1)Ovarian aging leads to diminished fertility, dysregulated endocrine signaling and increased chronic disease burden. These effects begin to emerge long before follicular exhaustion. Female humans experience a sharp decline in fertility around 35 years of age, which corresponds to declines in oocyte quality. Despite a growing body of work, the field lacks a comprehensive cellular map of the transcriptomic changes in the aging mouse ovary to identify early drivers of ovarian decline. To fill this gap we performed single-cell RNA sequencing on ovarian tissue from young (3-month-old) and reproductively aged (9-month-old) mice. Our analysis revealed a doubling of immune cells in the aged ovary, with lymphocyte proportions increasing the most, which was confirmed by flow cytometry. We also found an age-related downregulation of collagenase pathways in stromal fibroblasts, which corresponds to rises in ovarian fibrosis. Follicular cells displayed stress-response, immunogenic and fibrotic signaling pathway inductions with aging. This report provides critical insights into mechanisms responsible for ovarian aging phenotypes. The data can be explored interactively via a Shiny-based web application.Nature agingA single-cell atlas of the aging mouse ovary.PMC10798902P30 AG050911Pilot FundingS10 OD028479R01 AG069742Ocanas SRIsola JVVKo SKovats SAlberola-Ila JHense JDCarter HNCSchneider AMondal SAFreeman WMStout MBHubbart CRfalseA single-cell atlas of the aging mouse ovary.Ovarian aging leads to diminished fertility, dysregulated endocrine signaling and increased chronic disease burden. These effects begin to emerge long before follicular exhaustion. Female humans experience a sharp decline in fertility around 35 years of age, which corresponds to declines in oocyte quality. Despite a growing body of work, the field lacks a comprehensive cellular map of the transcriptomic changes in the aging mouse ovary to identify early drivers of ovarian decline. To fill this gap we performed single-cell RNA sequencing on ovarian tissue from young (3-month-old) and reproductively aged (9-month-old) mice. Our analysis revealed a doubling of immune cells in the aged ovary, with lymphocyte proportions increasing the most, which was confirmed by flow cytometry. We also found an age-related downregulation of collagenase pathways in stromal fibroblasts, which corresponds to rises in ovarian fibrosis. Follicular cells displayed stress-response, immunogenic and fibrotic signaling pathway inductions with aging. This report provides critical insights into mechanisms responsible for ovarian aging phenotypes. The data can be explored interactively via a Shiny-based web application.2024-01-01T00:00:00Z2024 Jan2026-03-27T16:37:19.794Z2025-04-04T19:21:35.549ZS-EPMC107989023820027210.1038/s43587-023-00552-5