重金属污染问题严重，我国儿童铅镉每周实际摄入量超过每周推荐摄入量的比例分别是30%和14%；铅镉均可损害神经干细胞增殖、分化和迁移的功能，与儿童智力发育损伤有关；LncRNA Pnky在大脑中特异性表达，可调控神经干细胞向神经元或胶质细胞分化。尚缺乏铅镉复合暴露与Pnky表达因果关联证据。据此我们依托上海优生儿童队列提出假说：铅镉复合暴露影响Pnky表达，由此Pnky调控神经干细胞发育的功能受损，对儿童神经发育产生影响。本课题依托上海优生队列，拟采用析因设计探讨宫内铅镉复合暴露对幼儿神经认知发育的影响；运用LncRNA测序结合生物信息学分析技术解释Pnky在胎盘中表达差异以及在铅镉复合暴露与神经认知发育关联中的作用。动物模型验证Pnky在铅镉复合暴露和神经干细胞发育损伤关联中的作用。本研究将以Pnky为新视点探讨铅镉复合暴露影响神经干细胞发育损伤机制，为其健康风险评估及其防控提供理论指导。

Heavy metal pollution is severe in China. Actual weekly intake of lead and cadmium among children aged 2-7 years in China are 30% and 14% higher than their provisional tolerable weekly intakes. Lead and cadmium exposure can affect the production, differentiation, and migration of neural stem cells (NSCs), and is associated with intellectual impairment in children. Pnky, a neural-specific long noncoding RNA (LncRNA) expressed in the brain, regulates the neural differentiation of NSCs into downstream lineages. However, evidence is lacking on the potential effects of co-exposure to lead and cadmium on Pnky expression. Based on the Shanghai Birth Cohort, we utilize a factorial experiment design to investigate the effects of prenatal co-exposure to lead and cadmium on the neurocognitive development in children. LncRNA sequencing along with bioinformatics analytic techniques will be used to explain the differential expression profiles of Pnky in placenta as well as its potential roles in the association between co-exposure to lead and cadmium and neurocognitive development. Animal model will be used to validate the roles of Pnky expression in lead and cadmium co-exposure induced NSC development defects. Our study will explore the new prospective mechanism of Pnky in lead and cadmium co-exposure related neurocognitive impairment in children, contributing theoretical guidance to health risk assessment and mitigation.