Epigenomics of rat born to dams fed a diet deficient in methyl group donors (MDD)

It is clearly established that the maternal diet during pregnancy can induce physiological and metabolic adaptations in the developing fetus which determine its susceptibility later in life to develop diabetes, obesity... The molecular and genomic mechanisms underlying the programming of the metabolic syndrome remain largely unknown but may involve resetting of epigenetic marks and fetal gene expression. We analyzed the profile of the liver methylome in 21-day-old rats born to mothers fed with a standard diet or a diet lacking methyl donor nutrients (Vitamin B12 and folates) during gestation and lactation. Modifications of DNA methylation were found in the promoter regions of 1,032 genes out of 14,981 genes. Bioinformatics analysis revealed that these genes are mainly involved in glucose and lipid metabolism, nervous system, coagulation, endoplasmic reticulum (ER) stress and mitochondrial function.现有研究已明确证实，妊娠期母体饮食可对发育中的胎儿产生生理与代谢层面的适应性改变，进而决定其日后罹患糖尿病、肥胖症等疾病的易感性。介导代谢综合征发育编程的分子与基因组机制目前仍未完全阐明，但可能涉及表观遗传标记的重置以及胎儿基因表达的调控。本研究对两组21日龄大鼠的肝脏甲基组（methylome）谱进行了分析：两组大鼠的母鼠在妊娠及哺乳期间分别喂食标准饲料，或缺乏甲基供体营养素（维生素B12与叶酸）的饲料。在检测的14981个基因中，共有1032个基因的启动子区域发生了DNA甲基化修饰。生物信息学分析显示，这些基因主要参与糖脂代谢、神经系统功能、凝血过程、内质网（ER）应激以及线粒体功能调控等生物学过程。