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  3. Epigallocatechin gallate alleviates mono-2-ethylhexyl phthalate-induced male germ cell pyroptosis by inhibiting the ROS/mTOR/NLRP3 pathway

Epigallocatechin gallate alleviates mono-2-ethylhexyl phthalate-induced male germ cell pyroptosis by inhibiting the ROS/mTOR/NLRP3 pathway

  • Toxicol In Vitro. 2023 Jun 5;105626. doi: 10.1016/j.tiv.2023.105626.
Yifan Hong 1,  Xiazhu Zhou 1,  Qi Li 1,  Jing Chen 1,  Yuexin Wei 2,  Lianju Shen 3,  Chunlan Long 4,  Shengde Wu 2,  Guanghui Wei 2
Affiliations

Affiliations

  • 1 Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
  • 2 Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
  • 3 Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China.
  • 4 Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatrics, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, PR China. Electronic address: 481113@hospital.cqmu.edu.cn.
PMID: 37286014 DOI: 10.1016/j.tiv.2023.105626
Abstract

Mono-2-ethylhexyl phthalate (MEHP) exposure is known to induce severe testicular injury via Reactive Oxygen Species (ROS). However, few effective treatments are available for the precise treatment of MEHP-induced germ cell damage. Epigallocatechin gallate (EGCG), one of the major Polyphenols in green tea, has potential antioxidant activity and can alleviate many diseases induced by oxidative stress. This study explored whether EGCG protects germ cells from MEHP-induced oxidative stress damage. Cells were treated with 400 μM MEHP and 60 μM EGCG for 24 h. EGCG reduced MEHP-induced ROS overgeneration in the spermatogonial cell line GC-1 and spermatocyte cell line GC-2. Western blotting and immunofluorescence showed that the MEHP+EGCG group exhibited lower nuclear factor (erythroid-derived 2)-like 2 (NRF2), heme oxygenase (decycling) 1 (HO-1), and superoxide dismutase (SOD) expression than the MEHP group. Moreover, activation of the mammalian target of rapamycin (mTOR) pathway was decreased. The expression of key factors of Pyroptosis was downregulated, and interleukin-10 (IL-10) expression was reduced. Additionally, Apoptosis was inhibited by EGCG. The findings indicate that EGCG protects against MEHP-induced germ cell Pyroptosis by scavenging ROS, suppressing the mTOR pathway, and inhibiting Pyroptosis. EGCG may thus be a potential treatment for MEHP-related spermatogenic dysfunction.

Keywords

EGCG; Germ cell; MEHP; Pyroptosis; mTOR.

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