Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model  

作　　者：Hao Zhang Xia Zha Yi Zheng Xiaoyun Liu Mabrouk Elsabagh Hongrong Wang Honghua Jiang Mengzhi Wang 

机构地区：[1]Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition,College of Animal Science and Technology,Yangzhou University,Yangzhou 225009,P.R.China [2]Joint International Research Laboratory of Agriculture and Agri‑Product Safety,Ministry of Education of China,Yangzhou University,Yangzhou 225009,P.R.China [3]Department of Animal Production and Technology,Faculty of Agricultural Sciences and Technologies,Niğde Omer Halisdemir University,Nigde 51240,Turkey [4]Department of Nutrition and Clinical Nutrition,Faculty of Veterinary Medicine,Kafrelsheikh University,KafrelSheikh,Egypt [5]Department of Pediatrics,Northern Jiangsu People’s Hospital,Clinical Medical College,Yangzhou University,Yangzhou 225001,China [6]State Key Laboratory of Sheep Genetic Improvement and Healthy Production,Xinjiang Academy of Agricultural Reclamation Science,Shihezi 832000,China

出　　处：《Journal of Animal Science and Biotechnology》2024年第1期201-217,共17页畜牧与生物技术杂志（英文版）

基　　金：supported by the fund for the National 14th Five-Year Plan Key Research and Development Program(2021YFD1600702);XPCC Agricultural Science and Technology Innovation Project(NCG202232);the Top Talents Award Plan of Yangzhou University(2020)。

摘　　要：Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,t

关 键 词：AUTOPHAGY Bisphenol A Endoplasmic reticulum stress Fetal growth restriction Inflammatory responses SHEEP 

分 类 号：S826[农业科学—畜牧学]