Protective effects of melatonin on DEHP-induced apoptosis and oxidative stress in prepubertal testes via the PI3K/AKT pathway

作者全名："Chen, Jiadong; Zhao, Tianxin; Zheng, Xiangqin; Kang, Lian; Wang, Junke; Wei, Yuexin; Wu, Yuhao; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde"

作者地址："[Chen, Jiadong; Zheng, Xiangqin; Kang, Lian; Wang, Junke; Wei, Yuexin; Wu, Yuhao; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing, Peoples R China; [Chen, Jiadong; Zheng, Xiangqin; Kang, Lian; Wang, Junke; Wei, Yuexin; Wu, Yuhao; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] Minist Educ Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Chen, Jiadong; Zheng, Xiangqin; Kang, Lian; Wang, Junke; Wei, Yuexin; Wu, Yuhao; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Chen, Jiadong; Zheng, Xiangqin; Kang, Lian; Wang, Junke; Wei, Yuexin; Wu, Yuhao; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] China Int Sci & Technol Cooperat Base Child Dev &, Chongqing, Peoples R China; [Chen, Jiadong; Zheng, Xiangqin; Kang, Lian; Wang, Junke; Wei, Yuexin; Wu, Yuhao; Shen, Lianju; Long, Chunlan; Wei, Guanghui; Wu, Shengde] Chongqing Key Lab Pediat Chongqing, Chongqing, Peoples R China; [Zhao, Tianxin] Guangzhou Med Univ, Guangzhou Woman & Childrens Med Ctr, Dept Pediat Urol, Guangzhou, Peoples R China; [Wei, Guanghui; Wu, Shengde] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing, Peoples R China; [Wu, Shengde] Chongqing Key Lab Children Urogenital Dev & Tissue, Room 806,Kejiao Bldg 6,136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China"

通信作者："Wu, SD (通讯作者)，Chongqing Key Lab Children Urogenital Dev & Tissue, Room 806,Kejiao Bldg 6,136,Zhongshan 2nd Rd, Chongqing 400014, Peoples R China."

来源：ENVIRONMENTAL TOXICOLOGY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001106535500001

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：apoptosis; di(2-ethylhexyl) phthalate; melatonin; oxidative stress; PI3K/AKT signaling pathway; prepubertal testes

摘要："Di(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, is one of the most common plasticizers and is widely used in various plastic products. DEHP induces apoptosis and oxidative stress and has been shown to have androgenic toxicity. However, the methods to combat DEHP-induced testicular damage and the mechanisms involved remain to be elucidated. In the present study, we used melatonin, which has strong antioxidant properties, to intervene in prepubertal mice and mouse Leydig cells (TM3) treated with DEHP or its metabolite mono(2-ethylhexyl) phthalate (MEHP). The results showed that melatonin protected against DEHP-induced testicular damage in prepubertal mice, mainly by protecting against DEHP-induced structural destruction of the germinal tubules and by attenuating the DEHP-induced decrease in testicular organ coefficients and testosterone levels. Transcriptomic analysis found that melatonin may attenuate DEHP-induced oxidative stress and apoptosis in prepubertal testes. In vitro studies further revealed that MEHP induces oxidative stress injury and increases apoptosis in TM3 cells, while melatonin reversed this damage. In vitro studies also found that MEHP exposure inhibited the expression levels of molecules related to the PI3K/AKT signaling pathway, and melatonin reversed this change. In conclusion, these findings suggest that melatonin protects against DEHP-induced prepubertal testicular injury via the PI3K/AKT signaling pathway, and provide a theoretical basis and experimental rationale for combating male reproductive dysfunction."

基金机构："Foundation for innovative Research Groups of the National Natural Science Foundation of China [82071632, cx2019030]"

基金资助正文："Foundation for innovative Research Groups of the National Natural Science Foundation of China, Grant/Award Numbers: 82071632, cx2019030"