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Adv."],"published-print":{"date-parts":[[2026,2,27]]},"abstract":"<jats:p>\n                    Environmental stressors\u2013induced male infertility has become a major public health issue. Sperm motility is the key to conception. However, the immunological mechanism for environmental stress\u2013induced sperm motility reduction remains unknown. Our experiments find that three classical environmental stressors, including lead, cadmium, and mercury, are the key heavy metals reducing sperm motility. We reveal that environmental stress induces epididymal macrophage senescence, whereas the clearance of above cells significantly alleviates environmental stress\u2013reduced sperm motility. In vivo and in vitro experiments further demonstrate that environmental stress induces macrophage senescence via down-regulating\n                    <jats:italic toggle=\"yes\">Foxo3<\/jats:italic>\n                    expression. Mechanistically, environmental stress increases the epididymal\n                    <jats:italic toggle=\"yes\">Foxo3 N<\/jats:italic>\n                    6-methyladenosine level and inhibits the FTO. Overexpression of\n                    <jats:italic toggle=\"yes\">Fto<\/jats:italic>\n                    in vitro and\n                    <jats:italic toggle=\"yes\">S<\/jats:italic>\n                    -adenosylhomocysteine supplementation in vivo alleviates environmental stress\u2013induced macrophage senescence. Together, these results suggest that epididymal macrophage senescence contributes to sperm motility decrease upon environmental stress. Clearing senescent epididymal macrophages will provide a previously unknown strategy for preventing male infertility.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea3591","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:58:20Z","timestamp":1772218700000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Epididymal macrophage senescence contributes to sperm motility decrease upon environmental stress"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2375-0288","authenticated-orcid":true,"given":"Xin-Run","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Toxicology, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei 230000, China."},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei 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