环境内分泌干扰物（（Environmental Endocrine Disruptors, EEDs）的健康效应已引起广泛关注。EEDs通过胎盘屏障，使胎儿处于宫内低剂量复合暴露中，故EEDs胚胎毒性研究是EEDs健康风险评价最关键的内容之一。因EEDs多呈现非单一剂量—效应，并在低剂量暴露时产生有害生物学效应，导致基于传统毒理学的评价与实际毒性作用相差甚远，故探求基于毒性机制的效应标志物是EEDs毒性评价的关键。本项目以不同性别人胚胎干细胞（embryonic stem cell，ES)诱导分化心肌细胞为靶器官发育模型进行EEDs低剂量暴露，从心肌细胞发育的信号通路和线粒体发育入手研究毒性效应和性别差异及其分子机制，探求毒性效应相关生物标志物及表达窗口期，并通过分析比较单一和复合暴露下毒性效应生物标志物的表达，揭示多种EEDs的相互作用模式，最终构建基于人ES的EEDs毒性效应评价模型。

Environmental endocrine disruptors (EEDs) and its adverse effects have been focused worldwide. The non-monotonic dose effect existed in EEDs, together with biological effect and gender-specific effect, result in great difference between the result of traditional toxicological evaluation and its real effect. Thus, locking a target organ and exploring the biomarker based on the mechanism of action (MOA) are crucial for EEDs assessment. According to previous study by using mouse embryonic stem cell (ES), we will establish a model of human ES by choosing cardiomyocyte as target organ, to clarify the MOA and gender-specific effect under low-dose EEDs exposure in this study. By tracing the change in key signaling pathway during cardiogenesis and development of mitochondria, we endeavor to find proper biomarker and sensitive exposure period, to set up a human ES-based model for EEDs assessment, and to provide a new tool for EEDs evaluation by mimicking human embryo development alternatively.