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With aging, both mouse and human ovaries become pro-fibrotic and stiff. However, whether follicles sense and respond to microenvironmental stiffness and affect folliculogenesis and oocyte quality independent of other aging-related factors is unknown. To address this question, we cultured mouse secondary follicles in alginate hydrogels that reproduce the stiffness of reproductively young and old mice. RNA-sequencing revealed that follicles respond rapidly to increased stiffness and exhibit enrichment in genes related to inflammation and extracellular matrix remodeling. Long-term culture in stiff hydrogels resulted in reduced follicle survival, granulosa cell viability, estradiol synthesis, and oocyte quality. To begin to determine how stiffness is transmitted within the follicle, we examined transzonal projections, which mediate granulosa cell\u2013oocyte communication and nutrient exchange. In stiff conditions, the number of transzonal projections decreased. Our findings demonstrate that follicles are highly mechanosensitive and that stiffness alone can trigger hallmarks of ovarian aging, including reduced follicle growth, reduced oocyte quality, and a fibroinflammatory phenotype potentially integrated into the oocyte via transzonal projections.<\/jats:p>","DOI":"10.1093\/reprod\/xaaf026","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T12:20:31Z","timestamp":1767615631000},"source":"Crossref","is-referenced-by-count":16,"title":["Increased stiffness mimicking ovarian aging induces a fibroinflammatory response in follicles and impairs oocyte quality"],"prefix":"10.1093","volume":"171","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0300-7657","authenticated-orcid":false,"given":"Sara","family":"Pietroforte","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine , St Louis, MO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8273-1434","authenticated-orcid":false,"given":"Farners","family":"Amargant","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine , St Louis, MO,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"2026021523215650000_xaaf026-B1","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1007\/s11357-024-01322-w","article-title":"Systemic low-dose anti-fibrotic treatment attenuates ovarian aging in the mouse","volume":"47","author":"Amargant","year":"2025","journal-title":"GeroScience"},{"key":"2026021523215650000_xaaf026-B2","doi-asserted-by":"publisher","first-page":"e13259","DOI":"10.1111\/acel.13259","article-title":"Ovarian stiffness increases with age in the mammalian ovary and depends on 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