Di-(2-ethylhexyl) phthalate induces ferroptosis in prepubertal mouse testes via the lipid metabolism pathway

作者全名："Wang, Xia; Li, Dinggang; Zheng, Xiangqin; Hong, Yifan; Zhao, Jie; Deng, Wei; Wang, Mingxin; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde"

作者地址："[Wang, Xia; Li, Dinggang; Zheng, Xiangqin; Hong, Yifan; Zhao, Jie; Deng, Wei; Wang, Mingxin; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing, Peoples R China; [Wang, Xia; Li, Dinggang; Zheng, Xiangqin; Hong, Yifan; Zhao, Jie; Deng, Wei; Wang, Mingxin; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ, Chongqing Key Lab Children Urogenital Dev & Tissue, Key Lab Child Dev & Disorders,Chongqing Key Lab Pe, Chongqing, Peoples R China; [Wu, Shengde] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China"

通信作者："Wu, SD (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China."

来源：ENVIRONMENTAL TOXICOLOGY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001112880200001

JCR分区：Q1

影响因子：4.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：di-(2-ethylhexyl) phthalate; ferroptosis; lipid metabolism; testicular damage

摘要："Di-(2-ethylhexyl) 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-induced testicular damage. In vivo study, we administered different doses of DEHP (0, 250, and 500 mg/kg/day) to male C57BL/6 mice from 22 and 35 days 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 (Fe2+) 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-chain 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-1 and monoethylhexyl phthalate (MEHP), MEHP-induced increases in Fe2+ 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-induced testicular damage."

基金机构：National Natural Science Foundation of China

基金资助正文：The authors wish to thank AJE () for language editing.