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Environ Int

Title:		"Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes"
Author(s):		Zhang H; Zheng Y; Liu X; Zha X; Elsabagh M; Ma Y; Jiang H; Wang H; Wang M;
Address:		"Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, PR China. Department of Animal Production and Technology, Faculty of Agricultural Sciences and Technologies, Nigde Omer Halisdemir University, Nigde 51240, Turkey; Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt. Department of Pediatrics, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, PR China. Electronic address: jianghonghua502@126.com. Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, PR China. Electronic address: hrwang@yzu.edu.cn. Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou 225009, PR China. Electronic address: mzwang@yzu.edu.cn"
Journal Title:		Environ Int
Year:		2023
Volume:		20230206
Issue:
Page Number:		107806 -
DOI:		10.1016/j.envint.2023.107806
ISSN/ISBN:		1873-6750 (Electronic) 0160-4120 (Linking)
Abstract:		"Bisphenol A (BPA)-induced oxidative stress (OS) and its potentially associated autophagy and apoptosis have not been studied previously in pregnant ewes. Accordingly, this study investigated the underlying mechanisms of BPA-induced autophagy and apoptosis in the placenta and primary trophoblasts of pregnant ewes exposed to BPA both in vivo and in vitro. In vivo experiment, pregnant Hu ewes (n = 8) were exposed to 5 mg/kg/d of BPA compared to control ewes (n = 8) receiving only corn oil from day 40 through day 110 of gestation. Exposure to BPA during gestation resulted in placental insufficiency, fetal growth restriction (FGR), autophagy, endoplasmic reticulum stress (ERS), mitochondrial dysfunction, OS, and apoptosis in type A placentomes. Regarding in vitro model, primary ovine trophoblasts were exposed to BPA, BPA plus chloroquine (CQ; an autophagy inhibitor) or BPA plus rapamycin (RAP; an autophagy activator) for 12 h. Data illustrated that exposure to BPA enhanced autophagy (ULK1, Beclin-1, LC3, Parkin, and PINK1), ERS (GRP78, CHOP10, ATF4, and ATF6) and apoptosis (Caspase 3, Bcl-2, Bax, P53) but decreased the antioxidant (CAT, Nrf2, HO-1, and NQO1)-related mRNA and protein expressions as well as impaired the mitochondrial function. Moreover, treatment with CQ exacerbated the BPA-mediated OS, mitochondrial dysfunction, apoptosis, and ERS. On the contrary, RAP treatment counteracted the BPA-induced trophoblast dysfunctions mentioned above. Overall, the findings illustrated that BPA exposure could contribute to autophagy in the ovine placenta and trophoblasts and that autophagy, in turn, could alleviate BPA-induced apoptosis, mitochondrial dysfunction, ERS, and OS. These results offer new mechanistic insights into the role of autophagy in mitigating BPA-induced placental dysfunctions and FGR"
Keywords:		Humans Animals Pregnancy Sheep Female *Placenta/metabolism *Fetal Growth Retardation/chemically induced Apoptosis Oxidative Stress Autophagy Bisphenol A Fetal growth restriction Placenta;
Notes:		"MedlineZhang, Hao Zheng, Yi Liu, Xiaoyun Zha, Xia Elsabagh, Mabrouk Ma, Yi Jiang, Honghua Wang, Hongrong Wang, Mengzhi eng Research Support, Non-U.S. Gov't Netherlands 2023/02/26 Environ Int. 2023 Mar; 173:107806. doi: 10.1016/j.envint.2023.107806. Epub 2023 Feb 6"