PMID- 37286014 OWN - NLM STAT- MEDLINE DCOM- 20230714 LR - 20230718 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 91 DP - 2023 Sep TI - Epigallocatechin gallate alleviates mono-2-ethylhexyl phthalate-induced male germ cell pyroptosis by inhibiting the ROS/mTOR/NLRP3 pathway. PG - 105626 LID - S0887-2333(23)00075-9 [pii] LID - 10.1016/j.tiv.2023.105626 [doi] AB - 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 muM MEHP and 60 muM 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. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Hong, Yifan AU - Hong Y AD - 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. FAU - Zhou, Xiazhu AU - Zhou X AD - 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. FAU - Li, Qi AU - Li Q AD - 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. FAU - Chen, Jing AU - Chen J AD - 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. FAU - Wei, Yuexin AU - Wei Y AD - 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. FAU - Shen, Lianju AU - Shen L AD - 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. FAU - Long, Chunlan AU - Long C AD - 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. FAU - Wu, Shengde AU - Wu S AD - 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. FAU - Wei, Guanghui AU - Wei G AD - 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. LA - eng PT - Journal Article DEP - 20230605 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Reactive Oxygen Species) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - BQM438CTEL (epigallocatechin gallate) RN - FU2EWB60RT (mono-(2-ethylhexyl)phthalate) RN - 6O7F7IX66E (phthalic acid) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 8R1V1STN48 (Catechin) SB - IM MH - Male MH - Humans MH - Reactive Oxygen Species/metabolism MH - *Pyroptosis MH - NLR Family, Pyrin Domain-Containing 3 Protein MH - Heme Oxygenase-1/metabolism MH - TOR Serine-Threonine Kinases MH - *Catechin/pharmacology OTO - NOTNLM OT - EGCG OT - Germ cell OT - MEHP OT - Pyroptosis OT - mTOR COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/06/08 01:08 MHDA- 2023/07/14 13:07 CRDT- 2023/06/07 19:25 PHST- 2023/03/09 00:00 [received] PHST- 2023/05/10 00:00 [revised] PHST- 2023/05/31 00:00 [accepted] PHST- 2023/07/14 13:07 [medline] PHST- 2023/06/08 01:08 [pubmed] PHST- 2023/06/07 19:25 [entrez] AID - S0887-2333(23)00075-9 [pii] AID - 10.1016/j.tiv.2023.105626 [doi] PST - ppublish SO - Toxicol In Vitro. 2023 Sep;91:105626. doi: 10.1016/j.tiv.2023.105626. Epub 2023 Jun 5.