百草枯是一种在我国乃至全世界范围内大量使用的除草剂，其慢性低剂量暴露所引发的神经发育毒性及其机制尚不明确。由于神经干细胞时空特异性的增殖和分化是神经系统正常发育的重要前提，因此本项目拟选择体外培养的人神经干细胞作为模型，以神经干细胞增殖和分化过程中的转录组产物及代谢组产物作为检测终点，结合生物信息学技术，综合探讨百草枯所致神经发育损伤过程中所涉及的神经发育毒作用通路及潜在生物标志。在此基础上，以离体培养的血管内皮细胞作为模型，观察百草枯暴露对血管内皮细胞紧密连接分子和功能性细胞因子的影响，进一步探讨血管内皮细胞在百草枯所致神经发育损伤中的作用。项目的实施不仅可以为百草枯的神经发育毒作用及其机制研究提供遗传学和代谢组学的信息，为体外神经发育毒性的评价和预测提供敏感特异的检测靶点，更能为体外评价神经发育毒性替代试验的推进提供理论参考。

Paraquat (PQ) is a widely used herbicide in China as well as all over the world. Yet, the impacts of PQ exposure on developing nervous system remain unclear.The temporally and spatially restricted proliferation and differentiation of neural stem cells are essential to the development of nervous system, thus in the current project we aim to investigate the effects of low-dose PQ on transcriptome and metabolome of human neural stem cells, and try to explicit the developmental neurotoxic pathway and biomarkers. In addition, we will investigate the roles of vascular endothelial cells in the developmental neurotoxicity (DNT) induced by PQ. This work will provide not only substantial genetic and metabolomic information for DNT mechanisms of PQ, but also valuable endpoints of in vitro models for DNT assessment.