X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl) phthalate-induced testis toxicity

作者全名："Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Long, Chunlan; Shen, Lianju; Zheng, Xiangqin; Li, Dinggang; Wang, Xia; Yu, Chenjun; Wu, Shengde; Wei, Guanghui"

作者地址："[Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Zheng, Xiangqin; Li, Dinggang; Wang, Xia; Yu, Chenjun; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Long, Chunlan; Shen, Lianju; Zheng, Xiangqin; Li, Dinggang; Wang, Xia; Yu, Chenjun; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Pediat Res Inst, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Long, Chunlan; Shen, Lianju; Zheng, Xiangqin; Li, Dinggang; Wang, Xia; Yu, Chenjun; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Children Urogenital Dev & Tissue, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Long, Chunlan; Shen, Lianju; Zheng, Xiangqin; Li, Dinggang; Wang, Xia; Yu, Chenjun; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Long, Chunlan; Shen, Lianju; Zheng, Xiangqin; Li, Dinggang; Wang, Xia; Yu, Chenjun; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Minist Educ, Key Lab Child Dev & Disorders, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Long, Chunlan; Shen, Lianju; Zheng, Xiangqin; Li, Dinggang; Wang, Xia; Yu, Chenjun; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing 400014, Peoples R China; [Hong, Yifan; Zhou, Xiazhu; Li, Qi; Chen, Jing; Wei, Yuexin; Long, Chunlan; Shen, Lianju; Zheng, Xiangqin; Li, Dinggang; Wang, Xia; Yu, Chenjun; Wu, Shengde; Wei, Guanghui] Chongqing Med Univ, Childrens Hosp, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing 400014, Peoples R China"

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

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001069561900001

JCR分区：Q1

影响因子：6.9

年份：2024

卷号：11

期号：2

开始页：935

结束页：951

文献类型：Article

关键词：Mitophagy; Pyroptosis; Testicular development; XBP1

摘要："As a widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP) is known to induce significant testicular injury. However, the potential mechanism and effects of pubertal exposure to DEHP on testis development remain unclear. In vivo, postnatal day (PND) 21 male rats were gavaged with 0, 250, and 500 mg/kg DEHP for ten days. Damage to the seminiferous epithelium and disturbed spermatogenesis were observed after DEHP exposure. Meanwhile, oxidative stress-induced injury and pyroptosis were activated. Both endoplasmic reticulum (ER) stress and mitophagy were involved in this process. Monoethylhexyl phthalate (MEHP) was used as the biometabolite of DEHP in vitro. The GC-1 and GC-2 cell lines were exposed to 0, 100 mM, 200 mM, and 400 mM MEHP for 24 h. Reactive oxygen species (ROS) generation, oxidative stress damage, ER stress, mitophagy, and pyroptosis were significantly increased after MEHP exposure. The ultrastructure of the ER and mitochondria was destroyed. X-box binding protein 1 (XBP1) was observed to be activated and translocated into the nucleus. ROS generation was inhibited by acetylcysteine. The levels of antioxidative stress, ER stress, mitophagy, and pyroptosis were decreased as well. After the administration of the ER stress inhibitor 4-phenyl-butyric acid, both mitophagy and pyroptosis were inhibited. Toyocamycininduced XBP1 down-regulation decreased the levels of mitophagy and pyroptosis. The equilibrium between pyroptosis and mitophagy was disturbed by XBP1 accumulation. In summary, our findings confirmed that DEHP induced a ROS-mediated imbalance in pyroptosis and mitophagy in immature rat testes via XBP1. Moreover, XBP1 might be the key target in DEHP-related testis dysfunction. 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)."

基金机构："National Natural Science Foundation of China [81771566, 82071632]; Post-graduate Research Innovation Project of Chongqing Medical University (China) [CYB22210]; Youth Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders (China) [YBRP-202114]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (No. 81771566, 82071632) , the Post-graduate Research Innovation Project of Chongqing Medical University (China) (No. CYB22210) , and the Youth Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders (China) (No. YBRP-202114)."