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
  • Daoyin Dong
  • E. Albert Reece
  • Peixin Yang
Reference work entry


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.


Maternal diabetes Embryopathy Neural tube defects Congenital heart defects miRNA DNA methylation Histone modifications 

List of Abbreviations


Apoptosis signal-regulating kinase 1


Congenital heart defect


CBP/p300-interacting transactivator with ED-rich tail 2


Claudin 1


Connective tissue growth factor




Diabetes mellitus


DNA methyltransferase


Endoplasmic reticulum


E26 avian leukemia oncogene 1, 5′ domain


GATA binding protein 4


Grainyhead like transcription factor 3


Glycogen synthase kinase-3 beta


Histone 3 lysine 14 acetylation


Histone 3 lysine 27 acetylation


Histone 3 lysine 56 acetylation


Histone 3 lysine 9 acetylation


Histone 3 lysine 9 trimethylation


Histone 4 lysine 16 acetylation


Insulin-like growth factor 1


Inositol-requiring enzyme 1 alpha


Myocyte enhancer factor 2C




msh homeobox 1


Methylenetetrahydrofolate reductase


Neural tube defect


Platelet activating factor acetyl hydrolase, isofrom 1b, subunit 1


Paired box 3




Signal transducer and activator of transcription 3


TNF receptor-associated factor 3


Thrombospondin 1


Tubby like protein 3


Thioredoxin-interacting protein


Zinc finger E-box binding homeobox 2




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Authors and Affiliations

  1. 1.Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Maryland School of MedicineBaltimoreUSA

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