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

扫码查看

原文链接

NETL
NSTL
万方数据

外文摘要：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 μM,200 μM,and 400 μM MEHP for 24 h.Reactive oxygen species(ROS)generation,oxidative stress damage,ER stress,mitophagy,and pyroptosis were significantly increased af-ter MEHP exposure.The ultrastructure of the ER and mitochondria was destroyed.X-box bind-ing 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,mito-phagy,and pyroptosis were decreased as well.After the administration of the ER stress inhib-itor 4-phenyl-butyric acid,both mitophagy and pyroptosis were inhibited.Toyocamycin-induced XBP1 down-regulation decreased the levels of mitophagy and pyroptosis.The equilib-rium 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.

外文关键词：

DEHPMitophagyPyroptosisTesticular developmentXBP1

作者：

Yifan Hong、Xiazhu Zhou、Qi Li、Jing Chen、Yuexin Wei、Chunlan Long、Lianju Shen、Xiangqin Zheng、Dinggang Li、Xia Wang、Chenjun Yu、Shengde Wu、Guanghui Wei

展开 >

作者单位：

Department of Urology,Children's Hospital of Chongqing Medical University,Chongqing 400014,China

Pediatric Research Institute,Children's Hospital of Chongqing Medical University,Chongqing 400014,China

Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering,Children's Hospital of Chongqing Medical University,Chongqing 400014,China

Chongqing Key Laboratory of Pediatrics,Children's Hospital of Chongqing Medical University,Chongqing 400014,China

Ministry of Education Key Laboratory of

Ministry of Education Key Laboratory of Child Development and Disorders,Children's Hospital of Chongqing Medical University,Chongqing 400014,Ch

Ministry of Education Key Laboratory of Child Development and Disorders,Children's Hospital of Chongqing Medical University,Chongqing 40

展开 >

基金：

国家自然科学基金国家自然科学基金Postgraduate Research Innovation Project of Chongqing Medical University(China)Youth Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders(China)

项目编号：

8177156682071632CYB22210YBRP-202114

出版年：

2024

DOI：

10.1016/j.gendis.2023.02.030

基因与疾病(英文)

ISSN：

年,卷(期)：2024.11(2)

参考文献量64