已经发现妊娠期宫内高糖环境或父亲高血糖可以通过影响精子的表观遗传产生子代糖代谢异常传代效应。而母亲高血糖是否可以通过影响卵子的表观遗传而发生糖代谢异常的传代效应还未研究。课题组前期在小鼠模型已经发现高血糖母亲的子一代在一年后出现了明显的糖代谢异常表型，同时其胚胎中与糖代谢相关的基因发生了差异甲基化修饰。本项目将利用动物模型，检测母亲高血糖对其产生的卵子、囊胚，及胎儿和成年子代胰岛的差异甲基化基因表达和microRNA差异表达，关注母源性印记基因的表达水平及相应差异甲基化区（DMR）甲基化状况；检测高糖环境下甲基转移酶（DNMT1，DNMT3a，DNMT3b）的水平，研究差异基因 DMR甲基化改变的机制是否由DNMTs表达调控异常所致。以揭示母体高糖环境通过卵子表观遗传改变子代发育程序，最终导致成年后患糖尿病风险增加的可能机制，为母亲高糖环境所致隔代发病效应实现源头控制提供理论基础。

Intrauterine or paternal hyperglycemia environment has been confirmed to increase risk of diabetes in offspring beyond genetic factors via altering the epigengenetics of sperms. However, it is unknown whether maternal hyperglycemia environment could increase the risk of impaired glucose tolerance in offspring. Our team previously found that maternal hyperglycemia environment, not gestational hyperglycemia, induced impaired glucose tolerance in one-year-old offspring.We also found that several genes related to glucose metabolism in these embryos were differentially methylated. In this project we will use animal hyperglycemic model to examine the levels of differentially methylated genes and microRNA, including maternal imprint gene Igf2 expression and methylation status of differential methylation region (DMR) in oocytes, embryos and islets of pancreas. Meanwhile, we will detect the levels of DNA methyltransferase （DNMT1, DNMT3a，DNMT3b）in hyperglycemia environment to explore whether the mechanism of methylation change is associated with abnormal expression and regulation of DNMTs. We are in the hope of revealing the probable mechanism of transgenerational effect of maternal hyperglycemia environment, providing theory basis for controlling the transgenarational influence by originally maternal hyperglycemia.