Enhanced glutathione production protects against zearalenone-induced oxidative stress and ferroptosis in female reproductive system

作者全名："Fu, Wei; Dai, Chao; Ma, Zifeng; Li, Qiao; Lan, Daoliang; Sun, Changpo; Wu, Xin; Li, Jian; Wang, Shujin"

作者地址："[Fu, Wei; Ma, Zifeng; Li, Qiao; Lan, Daoliang; Li, Jian] Southwest Minzu Univ, Key Lab Qinghai Tibetan Plateau Anim Genet Resourc, Minist Educ, Chengdu 610041, Peoples R China; [Dai, Chao; Wu, Xin] Chinese Acad Sci, Key Lab Agroecol Proc Subtrop Reg, Inst Subtrop Agr, Changsha 410125, Peoples R China; [Dai, Chao] Univ Chinese Acad Sci, Coll Adv Agr Sci, Beijing 100049, Peoples R China; [Sun, Changpo] Stand & Qual Ctr Natl Food & Strateg Reserv Adm, Beijing 100037, Peoples R China; [Fu, Wei] Southwest Minzu Univ, Key Lab Anim Sci Natl Ethn Affairs Commiss China, Chengdu 610041, Peoples R China; [Wang, Shujin] Chongqing Med Univ, Inst Life Sci, Chongqing 400032, Peoples R China"

通信作者："Li, J (通讯作者)，Southwest Minzu Univ, Key Lab Qinghai Tibetan Plateau Anim Genet Resourc, Minist Educ, Chengdu 610041, Peoples R China.; Wang, SJ (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing 400032, Peoples R China."

来源：FOOD AND CHEMICAL TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001174031700001

JCR分区：Q1

影响因子：3.9

年份：2024

卷号：185

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Mycotoxin; Zearalenone; Sus scrofa; Reproductive system; Oxidative stress; Ferroptosis; Glutathione

摘要："Zearalenone (ZEN, a widespread fusarium mycotoxin) causes evoked oxidative stress in reproductive system, but little is known about whether this is involved in ferroptosis. Melatonin, a well-known antioxidant, has demonstrated unique anti-antioxidant properties in several studies. Here, this study was aimed to investigate whether ZEN-induced oxidative stress in female pig's reproductive system was involved in ferroptosis, and melatonin was then supplemented to protect against ZEN-induced abnormalities in vitro cell models [human granulosa cell (KGN) and mouse endometrial stromal cell (mEC)] and in vivo mouse model. According to the results from female pig's reproductive organs, ZEN-induced abnormalities in vulvar swelling, inflammatory invasion and pathological mitochondria, were closely linked with evoked oxidative stress. Using RNA-seq analysis, we further revealed that ZEN-induced reproductive toxicity was due to activated ferroptosis. Mechanistically, by using in vitro cell models (KGN and mEC) and in vivo mouse model, we observed that ZEN exposure resulted in oxidative stress and ferroptosis in a glutathione-dependent manner. Notably, these ZEN-induced abnormalities above were alleviated by melatonin supplementation through enhanced productions of glutathione peroxidase 4 and glutathione. Herein, the present results suggest that potential strategies to improve glutathione production protect against ZEN-induced reproductive toxicity, including oxidative stress and ferroptosis."

基金机构："Natural Science Foundation of Sichuan Province [2022NSFSC1629]; Fundamental Research Funds for the Central Universities; Southwest Minzu University [2021PTJS20]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN202200445, KJQN202100410]"

基金资助正文："This study was financially supported by Natural Science Foundation of Sichuan Province (Grant No. 2022NSFSC1629 to Wei Fu) , ""the Fundamental Research Funds for the Central Universities "", Southwest Minzu University (Grant No. 2021PTJS20 to Wei Fu) , and the Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202200445, KJQN202100410 to Shujin Wang) ."