双酚A（BPA）替代物孕期暴露对胎盘发育的影响及其分子机制

双酚A（BPA）替代物（BPS、BPF和BPAF等）近年来广泛应用于工业生产，且具有与BPA类似的内分泌干扰效应。流行病学和实验研究表明BPA替代物孕期暴露会影响子代生长发育，而胎盘发育异常是衔接孕期污染物暴露与子代不良健康结局的关键环节。为此，本项目拟深入探讨孕期BPA替代物暴露对胎盘发育的影响及分子机制。（1）建立BPA替代物体外暴露和孕期暴露模型，检测模拟胎盘或孕鼠胎盘两侧污染物浓度，考察受试污染物的跨胎盘效率和胎儿的宫内生长状况；（2）结合形态观察、功能检测和关键因子表达，探究孕期污染物暴露对胎盘营养物质转运功能以及血管发育的影响；（3）通过体外和体内实验考察孕期污染物暴露后胎盘组织中甲状腺激素信号通路的响应特征，结合特异性干预实验，确定甲状腺激素信号通路在胎盘发育中的重要作用。本项目旨在为全面评估BPA替代物的毒理学效应和健康风险提供科学依据。

Several bisphenol analogues (BPS, BPF and BPAF), with endocrine disruption effects similar to BPA, have been produced in various applications. Epidemiological and experimental studies have shown that maternal bisphenol analogues exposure can affect the development of the offspring. In addition, abnormal placental development is the key bridge linked maternal exposure to pollutants and adverse health outcomes in the offspring. Our present study intend to explore the effects of maternal BPA analogues exposure on placental development and related molecular mechanisms. (1) We intend to establish in vitro and maternal exposure model of BPA analogues, detect the concentrations of pollutants in both sides of the in vitro model of placenta and placenta of the pregnant mice, and investigate the transplacental efficiency of these analogues and fetal growth in utero. (2) We try to explore the effects of maternal BPA analogues exposure on placental transport capacity for nutrients and vascular development by detecting placental function and evaluating the expression of key factor participated in these processes. (3) We examine the effects of maternal BPA analogues exposure on the thyroid hormone signaling pathway in the placenta in vitro and in vivo; combined with the specific thyroid receptor intervention experiment, we further determine the important role of thyroid hormone signaling pathway in the placental development. Our present study aims to provide a scientific basis for the comprehensive assessment of the toxicological effects and health risks of BPA analogues.