Embryopathy as a model for the epigenetics regulation of complications in diabetes: The roles of miRNA, DNA methylation, and histone modification in induction of diabetic embryopathy

Pregestational diabetes mellitus is a serious public health problem and a high-risk factor for diabetes-associated birth defects, such as neural tube defects (NTDs), congenital heart defects (CHDs), and susceptibility to postnatal diseases in the offspring. Over the past several decades, studies on the etiology of diabetic embryopathy have implicated epigenetic factors as an underlying cause for maternal diabetes-induced congenital developmental defects. Three epigenetic modalities - microRNA (miRNA), DNA methylation, and histone modification - are possible pathological pathways causing diabetic embryopathy. This chapter discusses the implication of epigenetic alterations in causing diabetic embryopathy. We highlight current studies which have demonstrated that maternal diabetes-altered miRNAs, DNA methylation, and histone modifications disturb embryonic developmental processes via inhibition of genes involved in stem cell proliferation and differentiation and activation of proapoptotic genes, thereby leading to embryonic malformation. Despite these promising studies, the detailed roadmap of how maternal diabetes causes epigenetic alterations which contribute to diabetic embryopathy is still elusive.