在双酚A（BPA）及其替代品甲状腺激素（TH）信号干扰和发育毒性的前期工作基础上，我们推测“BPA/BPF可能通过Notch信号和TH信号干扰神经干细胞稳态、影响其增殖和分化而导致神经发育毒性，而且这两个信号干扰可能存在交互作用”。本项目围绕这一假设，以非洲爪蛙为模型开展以下研究：1）在分子、细胞、脑组织学结构、神经行为等水平上识别BPF胚胎暴露对早期和后期神经发育的影响，并与BPA比较；2）探讨BPA/BPF对脑中TH信号和Notch信号的干扰作用及由此介导的对神经干细胞增殖和分化的效应；3）揭示BPA/BPF对脑中TH信号和Notch信号干扰的交互作用。通过以上研究，识别低剂量双酚类化合物胚胎暴露的神经发育毒性，在神经干细胞调控的层面揭示该类化合物神经发育毒性的分子机制，拓展对双酚类化合物神经毒性的认识，并为该类化合物的环境管理决策提供科学依据。

Based on previous work concerning thyroid hormone signaling disruption and developmental toxicities of bisphenol A (BPA) and its alternatives, we propose that “BPA and its alternatives may affect the proliferation and differentiation of neural stem cells and result in neurodevelopmental toxicity via disrupting TH signaling and Notch signaling with cross-talk”. Focusing on this proposal, we will carry out the following studies using Xenopus laevis as experimental animals: 1) To investigate neurodevelopmental toxicity of embryonic exposure to BPF in comparison with BPA; 2) To explore the effects of BPA/BPF on TH and Notch signaling in the brain, and the effects on the proliferation and differentiation of neural stem cells mediated by the two signaling pathways; 3) To reveal the cross-talk between TH and Notch signaling disruption by BPA/BPF. The above studies will identify neurodevelopmental toxicity of low concentration of bisphenol chemicals and clarify the molecular mechanisms of neurodevelopmental toxicity of BPA/BPF in term of the regulation for neural stem cells. This proposal will improve the understanding of neurotoxicity of bisphenol chemicals and provide scientific evidence for the management of these chemicals.