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  2. 1,2-Dichloroethane induces testicular pyroptosis by activating piR-mmu-1019957/IRF7 pathway and the protective effects of melatonin

1,2-Dichloroethane induces testicular pyroptosis by activating piR-mmu-1019957/IRF7 pathway and the protective effects of melatonin

  • Environ Int. 2024 Feb:184:108480. doi: 10.1016/j.envint.2024.108480.
Bingli Zhang 1 Yizhou Zhong 1 Jiaxin Du 1 Rongyi Ye 1 Bingchi Fan 1 Yanhong Deng 1 Ruobing Bai 1 Yu Feng 1 Xiaohong Yang 1 Yuji Huang 1 Boxuan Liang 1 Jiewei Zheng 2 Weifeng Rong 3 Xingfen Yang 1 Zhenlie Huang 4
Affiliations

Affiliations

  • 1 NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
  • 2 Department of Toxicology, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
  • 3 Institute of Chemical Surveillance, Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment, Guangzhou 510300, China.
  • 4 NMPA Key Laboratory for Safety Evaluation of Cosmetics, Guangdong Provincial Key Laboratory of Tropical Disease Research, Department of Toxicology, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address: huangzhenlie858252@smu.edu.cn.
Abstract

1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against Pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell Pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and Lactate Dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced Pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced Pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular Pyroptosis, and overexpression of piR-mmu-1019957 did not promote Pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular Pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.

Keywords

1,2-Dichloroethane; IRF7; Melatonin; PiRNAs; Pyroptosis; Reproductive toxicity.

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