title: Exploration of intrinsic and extrinsic apoptotic pathways in zearalenone-treated rat sertoli cells.
abstract: Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin produced mainly by Fusarium. ZEA causes reproductive disorders and is both cytotoxic and genotoxic in animals; however, little is known regarding the molecular mechanism(s) leading to ZEA toxicity. Sertoli cells are somatic cells that support the development of spermatogenic cells. The objective of this study was to explore the effects of ZEA on the proliferation, apoptosis, and necrosis of rat Sertoli cells to uncover signaling pathways underlying ZEA cytotoxicity. ZEA reduced the proliferation of rat Sertoli cells in a dose-dependent manner, as indicated by a CCK8 assay, while flow cytometry revealed that ZEA caused both apoptosis and necrosis. Immunoblotting revealed that ZEA treatment increased the ratio of Bax/Bcl-2, as well as the expression of FasL and caspases-3, -8, and -9, in a dose-dependent manner. Collectively, these data suggest that ZEA induced apoptosis and necrosis in rat Sertoli cells via extrinsic and intrinsic apoptotic pathways. This study provides new insights into the molecular mechanisms by which ZEA exhibits cytotoxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1731-1739, 2016.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Ming-Long
authors.initials: ML
authors.lastname: Xu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Bao-Ping
authors.initials: BP
authors.lastname: Guo
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Ya-Ru
authors.initials: YR
authors.lastname: Niu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiao
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
authors.forename: Yin-Xue
authors.initials: YX
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D053222:Fas Ligand Protein / Q000378:metabolism; D008297:Male; D009336:Necrosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D004968:Estrogens, Non-Steroidal; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D015025:Zearalenone; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: ZEA; apoptosis; extrinsic pathway; intrinsic pathway; sertoli cells