{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:13:41Z","timestamp":1785752021484,"version":"3.56.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T00:00:00Z","timestamp":1701734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Di\u2010(2\u2010ethylhexyl) phthalate (DEHP), a widely used plasticizer, has been shown to cause reproductive toxicity, but the precise mechanism remains unclear. This study aimed to investigate the possible molecular mechanism of DEHP\u2010induced testicular damage. In vivo study, we administered different doses of DEHP (0, 250, and 500\u2009mg\/kg\/day) to male C57BL\/6 mice from 22 and 35\u2009days after birth. We found that DEHP exposure induced histopathological alterations in prepubertal testes, and testicular lipidomics indicated notable alterations in lipid metabolism and significant enrichment of ferroptosis. Further tests showed that ferrous iron (Fe\n                    <jats:sup>2+<\/jats:sup>\n                    ) and malondialdehyde (MDA) levels significantly increased after DEHP exposure. Western blotting revealed that DEHP exposure reduced glutathione peroxidase 4 (GPX4) expression, and elevated acyl coenzyme A synthetase long\u2010chain member 4 (ACSL4) and lysophosphatidylcholine acyltransferase 3 (LPCAT3) expression. The in vitro results were consistent with the in vivo results. When Leydig cells and Sertoli cells were treated with ferrostatin\u20101 and monoethylhexyl phthalate (MEHP), MEHP\u2010induced increases in Fe\n                    <jats:sup>2+<\/jats:sup>\n                    and MDA levels, accumulation of lipid reactive oxygen species, downregulation of GPX4, and upregulation of ACSL4 and LPCAT3 were reversed. Collectively, our findings suggested that aberrant lipid metabolism and ferroptosis may be involved in prepubertal DEHP exposure\u2010induced testicular damage.\n                  <\/jats:p>","DOI":"10.1002\/tox.24065","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T03:46:17Z","timestamp":1701747977000},"page":"1747-1758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Di\u2010(2\u2010ethylhexyl) phthalate induces ferroptosis in prepubertal mouse testes via the lipid metabolism pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Xia","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International 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