{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:42:53Z","timestamp":1787013773742,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>With the increasing trend of delayed childbearing, the decline in oocyte quality associated with advanced maternal age has emerged as a pressing concern. However, the mechanism remains unclear, and effective strategies for improvement are currently lacking. Previously, we reported that the downregulation of the mevalonate pathway in aged granulosa cells (GCs) contributed to meiotic defects in oocytes, which may implicate farnesyl pyrophosphate\u2010mediated protein farnesylation. Nevertheless, the role of farnesylation in ovarian aging and its impact on oocytes requires further investigation. In this study, using cumulus\u2010oocyte complexes (COCs) from young and aged female mice, we observed impaired cumulus expansion and concurrent meiotic defects during aged oocyte maturation, accompanied by significantly reduced protein farnesylation in aged GCs. Furthermore, inhibiting farnesylation with FTI\u2010277 in young COCs recapitulated the aging phenotype, disrupting cumulus expansion and inducing meiotic defects similar to those in aged COCs. Conversely, restoring farnesylation via farnesol supplementation effectively ameliorated these deficits in both aged COCs (in vitro) and aged mice (in vivo). Proteomic analysis and experimental validation identified prostaglandin E2 synthase 2 (PTGES2) as a farnesylated protein. Mechanistically, age\u2010related decline in PTGES2 farnesylation in GCs reduces its endoplasmic reticulum localization and impairs prostaglandin E2 (PGE2) production, thereby compromising PGE2\u2010dependent cumulus expansion and oocyte maturation. Collectively, our findings highlight the detrimental effects of decreased farnesylation in aged GCs on oocyte quality and propose a potential therapeutic strategy for improving the developmental competence of aged oocytes.<\/jats:p>","DOI":"10.1111\/acel.70374","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T07:34:32Z","timestamp":1768203272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decreased\n                    <scp>PTGES2<\/scp>\n                    Farnesylation in Granulosa Cells Compromises\n                    <scp>PGE2<\/scp>\n                    \u2010Dependent Cumulus Expansion and Oocyte Maturation During Ovarian Aging"],"prefix":"10.1111","volume":"25","author":[{"given":"Sainan","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University  Nanjing China"},{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Qi","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanming","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2871-9653","authenticated-orcid":false,"given":"Huidan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bichun","family":"Guo","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Die","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicen","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Joint Institute of Nanjing Drum Tower Hospital for Life and Health, College of Life Science Nanjing Normal University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhen","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School Nanjing University  Nanjing 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