孕期补充叶酸作为一项预防出生缺陷的政策在我国得到推广，但是不同个体在叶酸摄取能力上差异较大，长期补充叶酸导致叶酸过量摄入的危害性尚有待于进一步的明确。前期，本课题组明确了叶酸过量摄入对雌性小鼠后代发育以及鼠胚胎干细胞干性、分化能力的影响，结果显示长期的叶酸过量摄入影响鼠胚胎干细胞干性和分化能力并导致房室隔缺损等小鼠后代胚胎发育异常，同时本课题组筛选到可能参与调控这一过程的重要基因——母系印迹长链非编码RNA Meg3，该基因与叶酸摄入异常调控小鼠胚胎干细胞干性以及心脏发育密切相关。在此基础之上，本课题将利用前期构建的小鼠模型以及鼠胚胎干细胞模型，在探讨叶酸补充安全标准的同时，深入研究叶酸过量摄入通过Meg3调控小鼠后代发育的具体机制以及相关分子作为标志物应用于指示叶酸过量摄入以及后代出生缺陷风险的可能性。本课题的研究成果将为更好地指导孕期叶酸补充提供理论和临床基础。

Folic acid (Folate, FA) supplementation has already been popularized in china as a policy to prevent birth defects. However, because of enormous individual difference in FA uptake, the harmfulness of the excessive FA intake induced by long-term supplementation of FA still need to be further clarified. Previously, we studied the effects of long-term excessive FA intake of female mice on the development of offspring and the stemness and pluripotent of mouse embryonic stem cells (mESCs). Our data showed that excessive FA intake would induce abnormal embryonic development in offspring of mice such as atrioventricular septal defect (AVSD). Then, the maternal imprinted long non-coding RNA Meg3, which was proved to be very important in regulating pluripotent of mESCs and cardiac development, was identified as one important actor involved in the regulation of excessive FA intake to the abnormal development of offspring of mice. On the basis of our previous studies, with pre-constructed mouse model and mESCs model, we will further study the exact mechanism of long-term excessive FA intake in regulating the development of offspring in mice by Meg3. Meanwhile, we will also discuss the safety standards for FA supplementation and the application of related molecules as candidate biomarkers in indicating excessive FA status in vivo or risk of birth defects in offspring. Our results may be helpful in better guide of clinical folate supplementation in prevention of birth defects by providing new strategy and theoretical basis.