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

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

doi:10.1016/j.gendis.2023.02.030

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

Full-length article | 更新时间：2024-02-04

- X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl) phthalate-induced testis toxicity
- Genes & Diseases Vol. 11, Issue 2, (2024)
- 作者机构：
  
  1. Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
  2. Department of Urology, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
  3. Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
  4. Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
  5. China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
  6. National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
  7. Pediatric Research Institute, Children's Hospital of Chongqing Medical University,Chongqing,China,400014
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2023.02.030
  CLC：
- Published：2024，
  
  Published Online：1 March 2024，
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Yifan Hong, Xiazhu Zhou, Qi Li, et al. X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl) phthalate-induced testis toxicity. [J]. Genes & Diseases 11(2).(2024)
DOI：

Yifan Hong, Xiazhu Zhou, Qi Li, et al. X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl) phthalate-induced testis toxicity. [J]. Genes & Diseases 11(2).(2024) DOI： 10.1016/j.gendis.2023.02.030.

摘要

Abstract

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 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. Toyocamycin-induced 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.

关键词

Keywords

DEHPMitophagyPyroptosisTesticular developmentXBP1

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