新兴全氟化合物替代品早期暴露对子代神经发育的影响及脂质代谢的作用机制

全氟化合物(PFAS)是一类在环境中广泛存在的持久性有机污染物，具有多脏器毒性，PFAS的神经毒性是目前研究热点之一。近期研究表明环境介质新兴PFAS替代品的浓度逐年上升，在人体的生物半衰期长于传统PFAS，但目前关于PFAS替代品暴露的人群流行病学研究还很匮乏。申请人课题组前期研究结果显示，新兴PFAS替代品的跨胎盘转运效率高于传统PFAS，且与不良出生结局显著正关联，提示新兴PFAS替代品的早期暴露可能影响儿童远期的生长发育。因此，本项目利用课题组建立的出生队列，采用人群生物监测与脂质组学技术相结合的研究策略，探讨暴露-脂质代谢-基因调控在PFAS替代品早期暴露影响神经发育的作用机制；通过动物模型分析污染物的跨胎盘转运的机体分布特征；明确脂质代谢物在脑部的作用靶点；结合转录组高通量测序筛查PFAS替代品神经毒性的敏感早期标志物，为开展PFAS替代品的环境风险管理和标准制定提供理论支持。

Perfluoroalkyl substances (PFAS) are one kind of persistent organic pollutants and can be widely detected in the environment. It has been shown that PFAS possess multi-organism toxicity and the neurotoxicity is a research hotspot. Recent studies have shown that the concentrations of PFAS alternatives have increased in the environment. Epidemiological studies are needed considering the halve life of PFAS alternatives in human body are longer than legacy PFAS. Our previous birth cohort studies have indicated that transplacental efficiency of PFAS alternatives was higher than legacy PFAS and was associated with adverse birth outcomes, indicating potential long-term health risks in children. Therefore, this project aims to investigate the associations between early exposure to PFAS alternatives and neurodevelopment in offspring. With the techniques of human biomonitoring and lipiomics, we will exam the associations between PFAS alternative exposure with lipid metabolism and gene regulation in the neurodevelopmental toxicity of PFAS alternatives. We will use animal model to characterize the transplacental distribution of PFAS alternatives in offspring. In addition, the MS-based technique of lipiomics ensures us to capture the deposition of differential lipids in brain. With the application of RNA-sequencing, we try to screen sensitive biomarkers associated with neurotoxicity of early life exposure to PFAS alternatives. Finally, findings in our project may help to conduct environmental risk management of PFAS alternatives and refine environmental policies governing their regulation.