{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T05:10:05Z","timestamp":1750137005097,"version":"3.41.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"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":["Immunol Cell Biol"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immune cells and blood metabolites play essential roles in the development of polycystic ovary syndrome (PCOS); however, it remains unclear whether blood metabolites mediate the causal relationship between immune cells and PCOS. This study aimed to delineate the causal relationships among immune cells, PCOS and potential blood metabolites through Mendelian randomization (MR). A two\u2010sample MR analysis was conducted using inverse variance weighting as the primary method to determine the causation between immune cells and PCOS risk. This was supplemented by a two\u2010step MR analysis to assess the mediating role of blood metabolites between immune cells and PCOS. In addition, a series of sensitivity analysis methods were employed to test the robustness of the results. We also performed a reverse MR to evaluate the possibility of reverse causal relationships. Our findings identified 22 immune cell phenotypes causally linked to PCOS, with 12 acting as risk factors and 10 as protective factors for PCOS. Furthermore, 45 blood metabolites or\u00a0ratios were causally related to PCOS. Mediation analysis revealed that X\u201025519 levels mediated 9.2% of the causal relationship between the absolute count of\u00a0CD28<jats:sup>\u2212<\/jats:sup>CD25<jats:sup>++<\/jats:sup> CD8<jats:sup>br<\/jats:sup> and PCOS. In addition, <jats:italic>N<\/jats:italic>\u2010acetylglucosamine\/<jats:italic>n<\/jats:italic>\u2010acetylgalactosamine levels and adenosine 5\u2032\u2010monophosphate levels mediated 6.7% and \u201311.1%, respectively, in the causation between naive DN(CD4<jats:sup>\u2212<\/jats:sup> CD8<jats:sup>\u2212<\/jats:sup>) %T\u00a0cell and PCOS. The aspartate\u2010to\u2010citrate ratio mediated 8.6% of the causal relationship between CD20<jats:sup>\u2212<\/jats:sup> CD38<jats:sup>\u2212<\/jats:sup> %B cells and PCOS. Finally, reverse MR studies did not identify any reverse causation between the 22 immune cell phenotypes and PCOS. This study elucidates the causal links between immune cells and PCOS, highlighting the potential roles of four blood metabolites in mediating the interaction between immune cells and PCOS, thus providing new targets for research and therapeutic interventions.<\/jats:p>","DOI":"10.1111\/imcb.70016","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T07:01:59Z","timestamp":1743231719000},"page":"461-472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal relationship between immune cells, metabolites and polycystic ovary syndrome identified by Mendelian randomization and mediation analyses"],"prefix":"10.1111","volume":"103","author":[{"given":"Lan","family":"Li","sequence":"first","affiliation":[{"name":"Gynecology Department The Second Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"},{"name":"College of lntegrative Medicine Hunan University of Traditional Chinese Medicine  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Mo","sequence":"additional","affiliation":[{"name":"College of lntegrative Medicine Hunan University of Traditional Chinese Medicine  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ximing","family":"Yu","sequence":"additional","affiliation":[{"name":"College of lntegrative Medicine Hunan University of Traditional Chinese Medicine  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"He","sequence":"additional","affiliation":[{"name":"Gynecology Department The Second Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Dai","sequence":"additional","affiliation":[{"name":"Gynecology Department The Second Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longlong","family":"Fan","sequence":"additional","affiliation":[{"name":"Gynecology Department The Second Affiliated Hospital of Hunan University of Chinese Medicine  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijie","family":"Yang","sequence":"additional","affiliation":[{"name":"College of lntegrative Medicine Hunan University of Traditional Chinese Medicine  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiping","family":"Liu","sequence":"additional","affiliation":[{"name":"College of lntegrative Medicine Hunan University of Traditional Chinese Medicine  Changsha Hunan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"World Health Organization.Polycystic ovary syndrome.https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/polycystic\u2010ovary\u2010syndrome. 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