{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T09:08:52Z","timestamp":1778576932488,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2022YFC2702505"],"award-info":[{"award-number":["2022YFC2702505"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Premature ovarian insufficiency (POI) impairs fertility and health in reproductive-age women, with autoimmune factors contributing to 4\u201330% of cases. To investigate immune dysregulation in POI, we developed two mouse models using pZP3 induction: regular immune (RE-POI) and enhanced immune (EN-POI) cycles. The EN-POI model exhibited stable, irreversible ovarian dysfunction, including disrupted estrous cycles, hormonal changes (elevated FSH, decreased AMH, and estradiol), follicular depletion, and infertility. Immune profiling demonstrated consistent T-lymphocyte imbalance across both RE-POI and EN-POI model groups, characterized by expanded splenic CD4+ T cells, diminished regulatory T cells, elevated systemic inflammatory cytokines, and ovarian fibrosis. Proteomic comparison between the control and EN-POI groups identified 198 differentially expressed proteins, mainly enriched in immune and inflammatory pathways. Based on these differential proteins, subsequent network analysis further identified six key hub proteins, namely Mmp9, Isg15, Ikbke, Siglec1, Pf4, and Cdkn1b. This study establishes a stable autoimmune POI model, elucidates T-cell imbalance with cytokine storm and fibrosis, and identifies key molecules linking immune abnormalities to ovarian failure, offering new insights into POI research.<\/jats:p>","DOI":"10.3390\/ijms27104270","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishment of an Autoimmune Premature Ovarian Insufficiency Mouse Model with Proteomic Analyses: An Exploratory Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Ying","family":"Tian","sequence":"first","affiliation":[{"name":"The Center for Clinical Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 212028, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Pei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiran","family":"Liu","sequence":"additional","affiliation":[{"name":"The Center for Clinical Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 212028, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feiyang","family":"Diao","sequence":"additional","affiliation":[{"name":"The Center for Clinical Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 212028, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41572-024-00547-5","article-title":"Premature ovarian insufficiency","volume":"10","author":"Touraine","year":"2024","journal-title":"Nat. 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