自噬减轻妊娠母羊胎盘凋亡、氧化应激和胎儿生长限制

IF 10.3 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES
Hao Zhang , Yi Zheng , Xiaoyun Liu , Xia Zha , Mabrouk Elsabagh , Yi Ma , Honghua Jiang , Hongrong Wang , Mengzhi Wang
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引用次数: 0

摘要

双酚A (BPA)诱导的氧化应激(OS)及其潜在相关的自噬和凋亡在怀孕母羊中尚未被研究过。因此,本研究在体内和体外研究BPA诱导妊娠母羊胎盘和原代滋养细胞自噬和凋亡的潜在机制。在体内试验中,从妊娠第40天至第110天,胡氏母羊(n = 8)与对照组母羊(n = 8)分别暴露于5 mg/kg/d的双酚a环境中。妊娠期暴露于BPA可导致A型胎盘不全、胎儿生长受限(FGR)、自噬、内质网应激(ERS)、线粒体功能障碍、OS和细胞凋亡。在体外模型中,将原代绵羊滋养细胞暴露于BPA、BPA加氯喹(CQ;一种自噬抑制剂)或BPA加雷帕霉素(RAP;数据表明,BPA暴露增强了自噬(ULK1、Beclin-1、LC3、Parkin和PINK1)、ERS (GRP78、CHOP10、ATF4和ATF6)和凋亡(Caspase 3、Bcl-2、Bax、P53),但降低了抗氧化剂(CAT、Nrf2、HO-1和NQO1)相关mRNA和蛋白的表达,并损害了线粒体功能。此外,CQ治疗加重了bpa介导的OS、线粒体功能障碍、细胞凋亡和ERS。相反,RAP处理抵消了上述bpa诱导的滋养细胞功能障碍。总的来说,研究结果表明BPA暴露可以促进羊胎盘和滋养细胞的自噬,而自噬反过来可以减轻BPA诱导的细胞凋亡、线粒体功能障碍、ERS和OS。这些结果为自噬在减轻bpa诱导的胎盘功能障碍和FGR中的作用提供了新的机制见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 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.

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来源期刊
Environment International
Environment International 环境科学-环境科学
CiteScore
21.90
自引率
3.40%
发文量
734
审稿时长
2.8 months
期刊介绍: Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review. It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.
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