Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S016041202300079X |
| _version_ | 1797868345624625152 |
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| author | Hao Zhang Yi Zheng Xiaoyun Liu Xia Zha Mabrouk Elsabagh Yi Ma Honghua Jiang Hongrong Wang Mengzhi Wang |
| author_facet | Hao Zhang Yi Zheng Xiaoyun Liu Xia Zha Mabrouk Elsabagh Yi Ma Honghua Jiang Hongrong Wang Mengzhi Wang |
| author_sort | Hao Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T23:54:27Z |
| format | Article |
| id | doaj.art-3da0bd0d6f294860b7444d518f499c2e |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-09T23:54:27Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-3da0bd0d6f294860b7444d518f499c2e2023-03-17T04:32:15ZengElsevierEnvironment International0160-41202023-03-01173107806Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewesHao Zhang0Yi Zheng1Xiaoyun Liu2Xia Zha3Mabrouk Elsabagh4Yi Ma5Honghua Jiang6Hongrong Wang7Mengzhi Wang8Laboratory 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 ChinaLaboratory 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 ChinaLaboratory 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 ChinaLaboratory 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 ChinaDepartment of Animal Production and Technology, Faculty of Agricultural Sciences and Technologies, Nĭgde Ömer Halisdemir University, Nigde 51240, Turkey; Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, EgyptLaboratory 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 ChinaDepartment of Pediatrics, Northern Jiangsu People’s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, PR China; Corresponding authors at: Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China (H. Wang and M. Wang).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; Corresponding authors at: Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China (H. Wang and M. Wang).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; Corresponding authors at: Laboratory of Metabolic Manipulation of Herbivorous Animal Nutrition, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, PR China (H. Wang and M. Wang).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.http://www.sciencedirect.com/science/article/pii/S016041202300079XAutophagyApoptosisBisphenol AFetal growth restrictionSheepPlacenta |
| spellingShingle | Hao Zhang Yi Zheng Xiaoyun Liu Xia Zha Mabrouk Elsabagh Yi Ma Honghua Jiang Hongrong Wang Mengzhi Wang Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes Environment International Autophagy Apoptosis Bisphenol A Fetal growth restriction Sheep Placenta |
| title | Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes |
| title_full | Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes |
| title_fullStr | Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes |
| title_full_unstemmed | Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes |
| title_short | Autophagy attenuates placental apoptosis, oxidative stress and fetal growth restriction in pregnant ewes |
| title_sort | autophagy attenuates placental apoptosis oxidative stress and fetal growth restriction in pregnant ewes |
| topic | Autophagy Apoptosis Bisphenol A Fetal growth restriction Sheep Placenta |
| url | http://www.sciencedirect.com/science/article/pii/S016041202300079X |
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