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J Anim Sci Biotechnol

Title:		Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model
Author(s):		Zhang H; Zha X; Zheng Y; Liu X; Elsabagh M; Wang H; Jiang H; Wang M;
Address:		"Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, P. R. China. Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou, 225009, P. R. 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, Egypt. Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, P. R. China. jianghonghua502@126.com. Department of Pediatrics, Northern Jiangsu People's Hospital, Clinical Medical College, Yangzhou University, Yangzhou, 225001, China. jianghonghua502@126.com. Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, P. R. China. mzwang@yzu.edu.cn. Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou, 225009, P. R. China. mzwang@yzu.edu.cn. State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural Reclamation Science, Shihezi, 832000, China. mzwang@yzu.edu.cn"
Journal Title:		J Anim Sci Biotechnol
Year:		2023
Volume:		20230911
Issue:		1
Page Number:		117 -
DOI:		10.1186/s40104-023-00919-z
ISSN/ISBN:		1674-9782 (Print) 2049-1891 (Electronic) 1674-9782 (Linking)
Abstract:		"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 400 mumol/L BPA, 400 mumol/L BPA + 0.5 mug/mL tunicamycin (Tm; ERS activator), 400 mumol/L BPA + 1 mumol/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, treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above. CONCLUSIONS: In general, the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs, and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine, OS, inflammatory responses, and autophagy. These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development"
Keywords:		Autophagy Bisphenol A Endoplasmic reticulum stress Fetal growth restriction Inflammatory responses Sheep;
Notes:		"PubMed-not-MEDLINEZhang, Hao Zha, Xia Zheng, Yi Liu, Xiaoyun Elsabagh, Mabrouk Wang, Hongrong Jiang, Honghua Wang, Mengzhi eng England 2023/09/11 J Anim Sci Biotechnol. 2023 Sep 11; 14(1):117. doi: 10.1186/s40104-023-00919-z"