{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:18Z","timestamp":1792790358925,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Physiology","reference-count":84,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Global Consortium for Reproductive Longevity & Equality","award":["GCRLE-1223"],"award-info":[{"award-number":["GCRLE-1223"]}]},{"award":["R01HD105752"],"award-info":[{"award-number":["R01HD105752"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R56AG101802"],"award-info":[{"award-number":["R56AG101802"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Thomas J. 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We hypothesized that post-ovulatory debris clearance becomes impaired with age and contributes to ovarian fibroinflammation. Using a CL-labeling system, we demonstrated that CLs from reproductively old mice show dysregulated regression, resulting in an accumulation of persistent CLs (pCLs) which appeared concurrently with ovarian multinucleated giant cells (MNGCs). Laser capture microdissection, RNA sequencing, and histological evaluation of CLs, pCLs, and MNGCs demonstrated that pCLs were focal hotspots of proinflammatory and debris-associated signatures enriched in lipids, extracellular matrix, and immune cells. Although pCLs retained luteal features, they were transcriptionally more similar to MNGCs than CLs. Consistent with this, an\n                  <jats:italic>ex vivo<\/jats:italic>\n                  CL model acquired MNGC-associated molecular features during extended culture, suggesting that pCLs may represent sites of MNGC formation. Culture of isolated follicles or ovarian stromal organoids with factors from MNGC-enriched explants induced compartment-specific fibroinflammatory responses. These findings provide novel mechanistic insight into ovarian aging, whereby post-ovulatory debris clearance is compromised with age, leading to pCL accumulation, MNGC formation, and a fibroinflammatory milieu.\n                <\/jats:p>","DOI":"10.64898\/2026.09.23.753904","type":"posted-content","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:20:16Z","timestamp":1790713216000},"source":"Crossref","is-referenced-by-count":0,"title":["Age-dependent dysregulated post-ovulatory debris clearance promotes ovarian fibroinflammation"],"prefix":"10.64898","author":[{"given":"Aubrey","family":"Converse","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline J.","family":"Perry","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta S.","family":"Dipali","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prianka H.","family":"Hashim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Gerton","sequence":"additional","affiliation":[{"name":"Stowers Institute for Medical Research, Kansas City, MO 64110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele T.","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, & Therapeutics, Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca E.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100313350760000_2026.09.23.753904v1.1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-16-0129"},{"key":"2026100313350760000_2026.09.23.753904v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13259"},{"key":"2026100313350760000_2026.09.23.753904v1.3","doi-asserted-by":"crossref","unstructured":"J. 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