{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:51:34Z","timestamp":1791445894403,"version":"4.3.3"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Diabetes mellitus adversely affects female reproductive health by inducing oxidative stress, impairing autophagy, and promoting fibrotic remodeling in ovarian and uterine tissues. Spermidine, a natural polyamine, has gained attention as an antioxidant and autophagy enhancer. This study aimed to investigate the potential protective role of spermidine against diabetes-induced reproductive injury in rats. Methods: Thirty adult female Wistar rats were randomly divided into three groups (n = 10 each): Control, Diabetes, and Diabetes + Spermidine. Diabetes was induced with streptozotocin (60 mg\/kg, i.p.). After confirmation of hyperglycemia (\u2265250 mg\/dL), rats received either saline or spermidine (40 mg\/kg\/day, oral gavage) for four weeks. At sacrifice, plasma anti-M\u00fcllerian hormone (AMH) levels were determined, and ovarian and uterine tissues were assessed histologically and biochemically for oxidative stress markers (GSH, MDA, Nrf2), autophagy proteins (LC3, Beclin-1), and fibrosis indicators (TGF-\u03b2, histological scoring). Results: Diabetic rats exhibited severe hyperglycemia, pronounced follicular and endometrial degeneration, increased fibrosis, reduced plasma AMH, depleted GSH, SOD, CAT, GPx and Nrf2, and elevated MDA (p &lt; 0.001). Spermidine treatment significantly mitigated these alterations, lowering glucose levels, alleviating histopathological injury, elevating the antioxidant defense (GSH, SOD, CAT, GPx) and the Nrf2 and decreasing MDA and TGF-\u03b2 concentrations (p &lt; 0.05 vs. Diabetes). Moreover, spermidine supplementation enhanced LC3 and Beclin-1 expression, suggesting improved autophagic activity. Conclusions: Spermidine counteracts diabetes-induced ovarian and uterine damage by reinforcing antioxidant defense, stimulating autophagy, and limiting fibrosis. These findings highlight spermidine as a promising adjunctive agent to support female reproductive health under diabetic conditions.<\/jats:p>","DOI":"10.3390\/antiox14111294","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:02:01Z","timestamp":1761670921000},"page":"1294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Protective Role of Spermidine Against Diabetes-Induced Ovarian and Endometrial Injury via LC3 and Beclin-1 Modulation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2480-1374","authenticated-orcid":false,"given":"Bakiye","family":"Akba\u015f","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical Faculty, Karadeniz Technical University, Trabzon 61080, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6513-0656","authenticated-orcid":false,"given":"G\u00fclseren","family":"Din\u00e7","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical Faculty, Karadeniz Technical University, Trabzon 61080, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6333-4919","authenticated-orcid":false,"given":"Ahmet","family":"Akba\u015f","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-2538","authenticated-orcid":false,"given":"Nadir Adnan","family":"Hac\u0131m","sequence":"additional","affiliation":[{"name":"Department of General Surgery, G\u00fcne\u015fli Erdem Hospital, Istanbul 34212, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-9298","authenticated-orcid":false,"given":"G\u00fcl\u00e7in","family":"Ercan","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Sultan 2. Abdulhamid Han Educational and Research Hospital, Istanbul Provincial Directorate of Health, Istanbul 34668, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4272-0562","authenticated-orcid":false,"given":"Hatice","family":"Ayg\u00fcn","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory, Biruni University Research Center (BAMER), Biruni University, Istanbul 34000, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-8428","authenticated-orcid":false,"given":"Oytun","family":"Erba\u015f","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biruni University Research Center (BAMER), Biruni University, Istanbul 34000, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s12020-024-03729-z","article-title":"Gonadal dysfunction in women with diabetes mellitus","volume":"85","author":"Zaimi","year":"2024","journal-title":"Endocrine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s10735-020-09880-x","article-title":"Histomorphological, VEGF and TGF-\u03b2 immunoexpression changes in the diabetic rats\u2019 ovary and the potential amelioration following treatment with metformin and insulin","volume":"51","author":"Ali","year":"2020","journal-title":"J. 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