{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T17:41:37Z","timestamp":1791481297483,"version":"4.3.4"},"reference-count":12,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Problem<\/jats:title>\n Polycystic ovary syndrome (PCOS) stands as a multifaceted endocrine disorder with implications beyond reproductive health, encompassing metabolic and immunological dimensions. This study delves into the immunological alterations within T cells in a murine PCOS model, unraveling novel insights into the molecular mechanisms contributing to T cell dysfunction.<\/jats:p>\n <\/jats:sec>\n \n Method of Study<\/jats:title>\n A PCOS model was established in mice, followed by isolating T cells. Isolated T cells were activated by anti\u2010CD3 and anti\u2010CD28 antibodies. Cytokine levels were determined by enzyme\u2010linked immunosorbent assay (ELISA) assay, and carboxyfluorescein succinimidyl ester (CFSE) dye was utilized for proliferation detection. Flow cytometry was utilized for analyzing exhaustion markers. RNA methylation analysis was determined by methylated RNA immunoprecipitation (Me\u2010RIP) assay.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In the PCOS mouse model, T cells exhibited a state of exhaustion, including impaired activation, reduced cytokine secretion, and decreased proliferative capacity. Particularly, the expression of T cell immunoreceptor with Ig and ITIM domain (TIGIT) molecules on the surface of T cells was significantly increased, which was associated with T cell exhaustion. The stability of TIGIT mRNA was enhanced due to the increased level of N6 RNA methylation, in which the methyltransferase\u2010like 3 (METTL3) methyltransferase played a key role. Experiments showed that by inhibiting N6\u2010methyladenosine (M6A) methylation or knocking out METTL3, the activation phenotype of PCOS T cells could be reversed, and cytokine secretion and proliferative capacity could be restored.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Although acknowledging study limitations, such as the murine model's partial recapitulation of human PCOS complexity, this research provides a foundation for future investigations into the specific molecular mechanisms governing T cell function and potential therapeutic targets within the N6 RNA methylation pathway.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/aji.70180","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T10:29:34Z","timestamp":1761388174000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunological Dynamics in PCOS T Cell Exhaustion TIGIT Upregulation Regulated by METTL3\u2010Mediated N6 RNA Methylation"],"prefix":"10.1111","volume":"94","author":[{"given":"Zhaowei","family":"Cai","sequence":"first","affiliation":[{"name":"Reproductive Center The Affiliated Dongguan Songshan Lake Central Hospital Guangdong Medical University Dongguan City Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongju","family":"Liu","sequence":"additional","affiliation":[{"name":"Reproductive Center The Affiliated Dongguan Songshan Lake Central Hospital Guangdong Medical University Dongguan City Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"Reproductive Center The Affiliated Dongguan Songshan Lake Central Hospital Guangdong Medical University Dongguan City Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liling","family":"Zhou","sequence":"additional","affiliation":[{"name":"Reproductive Center The Affiliated Dongguan Songshan Lake Central Hospital Guangdong Medical University Dongguan City Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyang","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Center The Affiliated Dongguan Songshan Lake Central Hospital Guangdong Medical University Dongguan City Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"He","sequence":"additional","affiliation":[{"name":"Reproductive Center The Affiliated Dongguan Songshan Lake Central Hospital Guangdong Medical University Dongguan City Guangdong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052734"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4092470"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/758656"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5894768"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2022.04.234"},{"issue":"4","key":"e_1_2_10_7_1","first-page":"1010","article-title":"Androgen\u2010Induced Cardiovascular Risk in Polycystic Ovary Syndrome: The Role of T Lymphocytes","volume":"13","author":"Moulana M.","year":"2023","journal-title":"Life (Basel)"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2015-1104"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-023-01147-9"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-022-01058-1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","unstructured":"Y.Qin T.Li H.Zhao Z.Mao C.Ding andY.Kang \u201cIntegrated Transcriptomic and Epigenetic Study of PCOS: Impact of Map3k1 and Map1lc3a Promoter Methylation on Autophagy \u201d (2021):620241.","DOI":"10.3389\/fgene.2021.620241"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.664843"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11071037"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.70180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T14:52:54Z","timestamp":1765464774000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.70180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,25]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/aji.70180"],"URL":"https:\/\/doi.org\/10.1111\/aji.70180","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,25]]},"assertion":[{"value":"2024-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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