skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Zearalenone induces apoptosis of rat Sertoli cells through Fas‐Fas ligand and mitochondrial pathway

Journal Article · · Environmental Toxicology
DOI:https://doi.org/10.1002/tox.22696· OSTI ID:1489294
 [1];  [2];  [2];  [2];  [2];  [2];  [2];  [1]; ORCiD logo [1]
  1. College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China, Jiangsu Co‐innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou Jiangsu China, Joint International Research Laboratory of Agriculture and Agri‐Product Safety of the Ministry of Education of China Yangzhou University Yangzhou Jiangsu China
  2. College of Veterinary Medicine Yangzhou University Yangzhou Jiangsu China, Jiangsu Co‐innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses Yangzhou Jiangsu China

Abstract Zearalenone (ZEA) is an estrogen‐like toxin produced by Fusarium that is widely found in cereals worldwide. In recent years, ZEA has been found to cause reproductive dysfunction in male animals, but the underlying mechanism remains unclear. This study examined the apoptosis of rat Sertoli cells induced by different concentrations (0, 5, 10, and 20 μmol/L) of ZEA via Fas‐Fas ligand and mitochondrial signaling pathway in vitro. Apoptosis rate was detected by flow cytometry. The mitochondrial membrane potential was detected by immunofluorescence assay and flow cytometry. Western Blot and qRT‐PCR were used to identify the signaling pathway. The results revealed that ZEA induced apoptosis of rat Sertoli cells, significantly reduced the transcription and expression of the anti‐apoptotic protein Bcl‐2, increased the transcription and expression of pro‐apoptotic proteins Bax and tBID, and Fas, FasL, FADD, and caspase‐8. ZEA also increased the activation of caspase‐8 and caspase‐9, and promoted the release of cytochrome C from mitochondria to cytoplasm. Moreover, addition of caspase‐8 inhibitor Z‐IETD‐FMK led to significant decrease in the mitochondrial membrane potential and apoptosis rate of the ZEA + Z‐IETD‐FMK group as compared to the ZEA treatment group. The release of cytochrome C from mitochondria to cytoplasm and the activation of caspase‐9 and caspase‐3 were significantly decreased in the ZEA + Z‐IETD‐FMK group. These results suggested that ZEA can induce apoptosis of rat Sertoli cells, activate the Fas‐Fas ligand signaling pathway and participate in the regulation of mitochondrial apoptosis pathway.

Sponsoring Organization:
USDOE
OSTI ID:
1489294
Journal Information:
Environmental Toxicology, Journal Name: Environmental Toxicology Vol. 34 Journal Issue: 4; ISSN 1520-4081
Publisher:
Wiley Blackwell (John Wiley & Sons)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 31 works
Citation information provided by
Web of Science

References (31)

Involvement of cyclin D1 and E2f1 in zearalenone-induced DNA damage in testis of rats journal November 2015
Crocin protects human embryonic kidney cells (HEK293) from α- and β-Zearalenol-induced ER stress and apoptosis journal April 2016
Death Receptors: Signaling and Modulation journal August 1998
Involvement of the Fas and Fas ligand in testicular germ cell apoptosis by zearalenone in rat journal January 2010
A Novel Protein That Interacts with the Death Domain of Fas/APO1 Contains a Sequence Motif Related to the Death Domain journal April 1995
Participation of the Fas-Signaling System in the Initiation of Germ Cell Apoptosis in Young Rat Testes after Exposure to Mono-(2-Ethylhexyl) Phthalate journal November 1999
Influence of in vitro exposure to mycotoxin zearalenone and its derivatives on swine sperm quality journal August 2008
Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease journal December 2005
The TNF and TNF Receptor Superfamilies journal February 2001
Zearalenone inhibits testosterone biosynthesis in mouse Leydig cells via the crosstalk of estrogen receptor signaling and orphan nuclear receptor Nur77 expression journal June 2014
Exploration of Bcl-2 family and caspases-dependent apoptotic signaling pathway in Zearalenone-treated mouse endometrial stromal cells journal August 2016
The mycotoxin Zearalenone induces apoptosis in human hepatocytes (HepG2) via p53-dependent mitochondrial signaling pathway journal October 2008
The biochemistry of apoptosis journal October 2000
Deletion of the BH1 Domain of Bcl-2 Accelerates Apoptosis by Acting in a Dominant Negative Fashion journal March 2003
Zearalenone induces apoptosis and necrosis in porcine granulosa cells via a caspase-3- and caspase-9-dependent mitochondrial signaling pathway journal January 2012
Occurrence, detection and detoxification of mycotoxins journal November 2015
Zearalenone impairs the male reproductive system functions via inducing structural and functional alterations of sertoli cells journal March 2016
Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells journal December 2010
Effects of PFNA exposure on expression of junction-associated molecules and secretory function in rat Sertoli cells journal November 2010
Donor Sertoli cells transplanted into irradiated rat testes stimulate partial recovery of endogenous spermatogenesis journal March 2009
Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis journal August 1998
Regulation of death receptor-induced apoptosis induced via CD95/Fas and other death receptors journal February 2011
The influence of the mycotoxins deoxynivalenol and zearalenol on in vitro maturation of pig oocytes and in vitro culture of pig zygotes journal December 2002
Involvement of the Fas/FasL pathway in the pathogenesis of germ cell tumours of the adult testis journal January 2002
Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell Death journal June 1996
Effect of lead on Sertoli–germ cell coculture of rat journal July 2000
Programmed Cell Death in Animal Development journal February 1997
Prognostic Significance of Soluble fas in the Serum of Patients with Bladder Cancer journal August 1998
FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis journal May 1995
The influence of N-acetyl-l-cysteine on damage of porcine oocyte exposed to zearalenone in vitro journal December 2015
Dose-response effects of estrogenic mycotoxins (zearalenone, alpha- and beta-zearalenol) on motility, hyperactivation and the acrosome reaction of stallion sperm journal January 2011