孕期肥胖(PO)可引起子代中枢神经系统(CNS)发育异常，其发生机理至今尚不清楚。我们前期研究发现，PO胚鼠的神经干细胞(NSCs)增值分化失调；且DNA甲基化和H3K27三甲基化可共同导致多个调控基因失活，参与的酶包含了DNMT1、EZH2和HDAC1(均为PcG蛋白复合体组分)，提示PcG蛋白对NSCs增值分化相关基因的调控可能是PO胚胎CNS发育异常的重要原因，其确切的分子机制有待于进一步论证。本项目拟在此基础上：(1)系统观察PO胚胎CNS发育情况及在体、离体NSCs增值分化模式；(2)探讨PcG蛋白介导的表观遗传网络的调控作用及作用机制，进一步揭示PO致胚胎神经系统发育异常的分子机理。课题的完成将对提供PO胚胎神经损伤早期诊断标记物及设计特异的表观遗传药物具有重要的理论价值和临床意义。

Pregnancy obesity (PO) can cause developmental abnormalities of central nervous system (CNS) in the offsprings, however, the underlying mechanism is still unclear. Our previous study found that the neural stem cells (NSCs) from PO embryonic mice exhibited dysregulation in their proliferation and differentiation; and DNA methylation and H3K27 trimethylation caused inactivation of a number of regulatory genes, involving DNMT1, EZH2 and HDAC1 (All of them are components of PcG protein complex), suggesting that the regulatory role of PcG proteins in NSC proliferation and differentiation associated genes may be an important reason for PO embryonic CNS abnormalities. The exact molecular mechanism remains to be demonstrated. The project intends to do the followings: (1) observe PO embryonic CNS development, and proliferation and differentiation of NSCs in vivo and in vitro; (2) investigate the role and mechanism of the epigenetic network mediated by PcG proteins, further revealing the molecular mechanism of PO-induced embryonic nervous system abnormalities. This project will provide diagnostic markers as well as help to design specific epigenetic drugs for PO embryonic nervous system damage.