Zearalenone induces apoptosis and autophagy by regulating endoplasmic reticulum stress signalling in porcine trophectoderm cells
摘要Zearalenone(ZEA),a mycotoxin produced mainly by fungi belonging to Fusarium species in foods and feeds,causes a serious hazard to humans and animals.Numerous studies have revealed that ingesting ZEA can disrupt the reproductive function and impair the reproductive process in animals.This exper-iment was to investigate the toxicological effect and the mechanism of ZEA exposure on reproduction in pigs during early stages of pregnancy.In the present study,we treated with 0 to 80 μmol/L ZEA for 12 or 24 h in trophoblast ectoderm(pTr)cells.The results showed that ZEA had significantly decreased cell proliferation(P<0.05),which was accompanied by DNA damage-related cell cycle arrest at G2/M phase,activation of the apoptosis and endoplasmic reticulum(ER)stress,as well as impairment of barrier function(P<0.05).Western blot analysis and transmission electron microscopy(TEM)showed that exposure to ZEA can activation of autophagy in pTr cells.Importantly,pretreatment with chloroquine(CQ)or 3-methyladenine(3-MA)led to increased apoptosis in pTr cells.Interestingly,pTr cells pretreated with 4-phenylbutyric acid(4-PBA),an inhibitor of ER stress,resulted in reduced cell death in pTr cells,indicating a critical role for ER stress in the activation of autophagy.In conclusion,these results reveal that ZEA-triggered ER stress is critical for the cell fate decision of pTr cells during early porcine em-bryonic development.Application of small molecules with ability of blocking ER stress might be ther-apeutic option to reduce the deleterious effect of ZEA in pregnant animals.
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