{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:21:52Z","timestamp":1787664112545,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515010874"],"award-info":[{"award-number":["2024A1515010874"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic epididymo\u2010orchitis contributes significantly to male infertility through immune cell infiltration and pro\u2010inflammatory cytokine elevation. High glucose intake promotes Th17 differentiation and autoimmunity, but its effects on autoimmune testicular inflammation remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To determine whether chronic high glucose supplementation exacerbates experimental autoimmune epididymo\u2010orchitis (EAEO), impairs spermatogenesis, and drives CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell dysregulation, particularly Th17 polarization, in the reproductive tract.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      EAEO was induced in male C57BL\/6 mice with or without chronic 10% glucose supplementation in drinking water. Sperm parameters, ROS levels, apoptosis, and histopathology were evaluated. CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell subsets (Th1, Th17, Treg, TNF\u2010\u03b1\n                      <jats:sup>+<\/jats:sup>\n                      effector memory) were quantified by flow cytometry in testis, epididymis, spleen, and testicular inguinal lymph nodes (iLN) at days 30, 60, and 90 post\u2010immunizations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High glucose intake accelerated EAEO progression, markedly worsening sperm concentration and motility, elevating sperm ROS, increasing germ cell apoptosis, and causing severe histopathological damage. In the reproductive tract, glucose induced an upward trend of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells and late\u2010phase selective Th17 skewing (days 60\u201390), with significant IL\u201017A\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      Teff increases and accompanying TNF\u2010\u03b1\n                      <jats:sup>+<\/jats:sup>\n                      CD4\n                      <jats:sup>+<\/jats:sup>\n                      CD44\n                      <jats:sup>+<\/jats:sup>\n                      Teff upregulation, while IFN\u2010\u03b3\n                      <jats:sup>+<\/jats:sup>\n                      Th1 responses remained modest. These pro\u2010inflammatory changes were strictly localized, with no significant Th17, Th1, Treg, or TNF\u2010\u03b1 alterations in spleen or iLN.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>\n                      Chronic high glucose exacerbates EAEO by intensifying oxidative stress, apoptosis, and tissue injury while promoting a late\u2010phase, tissue\u2010restricted Th17\u2010biased CD4\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell response in the testis and epididymis. These findings reveal a metabolic\u2010immune axis that may accelerate immune\u2010mediated male subfertility via localized Th17 mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/aji.70300","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T16:22:12Z","timestamp":1785342132000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High Glucose Supplementation Aggravates Experimental Autoimmune Epididymo\u2010orchitis via Localized Th17 Skewing in the Male Reproductive Tract"],"prefix":"10.1111","volume":"96","author":[{"given":"Jin\u2010Chuan","family":"Liu","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Fertility Regulation Center of Assisted Reproduction and Embryology The University of Hong Kong \u2013 Shenzhen Hospital  Shenzhen China"},{"name":"Department of Obstetrics and Gynecology the University of Hong Kong  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