妊娠期糖尿病（GDM）是妊娠期重要的代谢性疾病，可造成不良妊娠结局并危及胎儿健康。表观遗传学机制在GDM宫内高糖环境致子代不良结局中扮演重要角色。我们前期工作中在妊娠小鼠模型及妊娠期糖尿病患者血清样本中筛选出差异表达的microRNA, 其中miR221/222变化最为显著，且miR221/222在全身各组织广泛表达。靶基因预测及验证实验发现，miR221/222过表达可抑制细胞增殖相关基因PTEN和P27表达。结果表明miR221/222是妊娠前后以及妊娠糖尿病病理过程中变化明显的高度保守性microRNA, 极有可能通过调控下游靶基因表达影响子代发育及代谢。本项目旨在前期重要发现的基础上，应用临床生物样本和妊娠期糖尿病小鼠模型，从体内、体外水平探讨妊娠期糖尿病宫内高糖环境影响子代生长发育的miR221/222表观遗传调控机制，为宫内不良环境所致子代疾病发生实现源头控制提供理论基础。

Gestational diabetes mellitus (GDM) is an important metabolic disease affecting pregnant women and fetal health. Epigenetic mechanism plays a key role in fetal adverse outcomes resulted from intrauterine hyperglycemia environment of women with GDM. Nevertheless,the exact mechanism is still unknown. In our previous study, we have screened differentially expressed microRNA in the serum speciemen of patients with GDM or pregnant mouse model, compared with their normal controls. Of note, miR221/222 was the most changed microRNA in GDM or during pregnancy. Moreover, we found that miR221/222 is ubiquitiously expressed and highly conserved among different species. By target gene predicting and validation experiment, we further demonstrated that miR221/222 overexpression inhibited the expression of cell proliferation-related genes, PTEN and P27. Taken together, miR221/222 expression is dramaticly changed during pregnancy and in the pathological process of GDM.It is most likely that miR221/222 deregulation in GDM influences fetal growth and metablism by regulating the expression of downstream target genes. In this project we intend to utilize clinical samples and GDM mouse model to explore the miR221/222 involved epigenetic mechanism underlying the impact of intrauterine hyperglycemia environment on the development and metabolic abnormalities in the offspring in vivo and in vitro. This study will provide new evidence for the molecular mechanism of intrauterine environment inducing offsrping diseases.