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

被引：3

作者：

Wang, Xia ^{[1
,2
]}

Li, Dinggang ^{[1
,2
]}

Zheng, Xiangqin ^{[1
,2
]}

Hong, Yifan ^{[1
,2
]}

Zhao, Jie ^{[1
,2
]}

Deng, Wei ^{[1
,2
]}

Wang, Mingxin ^{[1
,2
]}

Shen, Lianju ^{[1
,2
]}

Long, Chunlan ^{[1
,2
]}

Wei, Guanghui ^{[1
,2
]}

Wu, Shengde ^{[1
,2
,3
]}

机构：

[1] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing, Peoples R China

[2] 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

[3] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China

来源：

ENVIRONMENTAL TOXICOLOGY | 2024年 / 39卷 / 03期

基金：

中国国家自然科学基金;

关键词：

di-(2-ethylhexyl) phthalate; ferroptosis; lipid metabolism; testicular damage; DI(2-ETHYLHEXYL)PHTHALATE DEHP; EXPOSURE;

D O I：

10.1002/tox.24065

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

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.

引用

页码：1747 / 1758

页数：12