title: Zearalenone induces apoptosis and cytoprotective autophagy in primary Leydig cells.
abstract: Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin found in several food commodities worldwide. ZEA causes reproductive disorders, genotoxicity, and testicular toxicity in animals. However, little is known about the functions of apoptosis and autophagy after exposure to ZEA in Leydig cells. This study investigated the effects of ZEA on rat Leydig cells. Results showed that ZEA at different doses significantly inhibited the growth of Leydig cells by inducing apoptosis. ZEA treatment upregulated Bax expression, promoted cytochrome c release into the cytosol, and triggered mitochondria-mediated apoptosis. Consequently, caspase-9 and downstream effector caspase-3 were activated, followed by the cleavage of poly(ADP-ribose) polymerase (PARP), resulting in Leydig cell apoptosis. ZEA treatment also upregulated LC3-II and Beclin-1 expression, suggesting that ZEA induced a high level of autophagy. Pretreatment with chloroquine (an autophagy inhibitor) and rapamycin (an autophagy inducer) increased and decreased the rate of apoptosis, respectively, in contrast to other ZEA-treated groups. Autophagy delayed apoptosis in the ZEA-treated Leydig cells. Therefore, autophagy may prevent cells from undergoing apoptosis by reducing ZEA-induced cytotoxicity.
authors: College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China.
authors: Yajun
authors: Y
authors: Wang
authors: College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China.
authors: Wanglong
authors: W
authors: Zheng
authors: College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China.
authors: Xiaojiao
authors: X
authors: Bian
authors: College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China.
authors: Yan
authors: Y
authors: Yuan
authors: College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China.
authors: Jianhong
authors: J
authors: Gu
authors: College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China.
authors: Xuezhong
authors: X
authors: Liu
authors: College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China.
authors: Zongping
authors: Z
authors: Liu
authors: College of Veterinary Medicine, Yangzhou University, 12 Wenhui East Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China. Electronic address: jcbian@yzu.edu.cn.
authors: Jianchun
authors: J
authors: Bian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D015025:Zearalenone / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D053148:Caspase 3; D053453:Caspase 9; D045304:Cytochromes c; D008869:Microtubule-Associated Proteins; D011065:Poly(ADP-ribose) Polymerases; D015025:Zearalenone; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat
keywords: Apoptosis; Autophagy; Leydig cells; Zearalenone