妊娠糖尿病（Gestational diabetes mellitus，GDM）是在怀孕时被首次检测到的葡萄糖不耐受现象，流行病学调查和实验结果表明GDM导致的宫内生长受限与新生儿成年后的某些疾病，包括2型糖尿病和心血管疾病等有着密切的联系。目前，GDM已经成为妊娠过程中最常见的并发症之一，其发病率在包括中国在内的全世界范围内快速增长。近来，下一代测序的发展催生了一种基于测序技术的全基因组表观遗传学方法，可以全面、客观的对基因组的表观修饰进行研究。在本项目中，我们将使用甲基化敏感的酶切计数法（MSCC），联合下一代测序技术研究GDM和健康产妇分娩后的脐带血的全基因组甲基化谱。对于在两组间甲基化程度存在差异的基因在独立的样品中进行验证，并利用小鼠模型对GDM影响后代发育和疾病这一过程中关键的基因进行初步的功能研究，为理解GDM和成年后疾病之间的联系，减少GDM对于子代的负面影响奠定理论基础。

Gestational diabetes mellitus (GDM) was defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Strong epidemiological and experimental evidence indicates a link between intrauterine growth restriction in GDM and adult diseases, such as type 2 diabetes and cardiovascular disease. Until now, GDM becoming one of the most common complications of pregnancy and it's incidence increasing rapidly worldwide, including China. Recently, the advances in next generation sequencing (NGS) technologies had enabled a powerful sequencing based method to interrogate whole genome epigenetic modifications and provide a comprehensive and unbiased view of the epigenome. Here we will use the methylation sensitive enzyme HpaII based methyl-sensitive cut counting (MSCC) method, together with NGS, to create a genome-scale methylation profile of offspring's umbilical cord blood of GDM and healthy pregnant women. And then verify those genes showed different methylation levels in these two groups in additional independent individuals. For those key genes in the early life programming and embryonic epigenetic modification, we will conduct a preliminary functional studies using mice model. Our studies may provide a great help in understanding the relationship between GDM and adult diseases, and provide the theoretic foundation in mitigating the negative impact of GDM to offspring.