Epigenetic modifications and gestational diabetes mellitus

Gestational diabetes mellitus (GDM), which is characterized by glucose intolerance first diagnosed during pregnancy, is one of the most common pregnancy complication. It is now affecting approximately 14% of pregnancies worldwide, and its prevalence continues to increase. Although GDM usually resolves after delivery, it may have several long-lasting health consequences, such as increased risk for type 2 diabetes mellitus and cardiovascular disease, on the mother as well as on the offspring. An increasing body of evidences supports the notion that experiencing an adverse intrauterine environment, especially when due to maternal hyperglycemia, can affect cellular and organ systems during the early life of the offspring and interact with postnatal environmental and lifestyle factors to define metabolic disease risk. The concept of lasting consequences of early-life environmental exposure for later disease risk is widely known as “fetal programming”, but the involved mechanisms are still not completely known. Compelling evidences point to the epigenetic processes as an important mechanism underpinning lasting effects on the offspring. The epigenetic processes, which include DNA methylation, the establishment of chromatin states by histones modifications and non-coding RNAs regulation, are able to modulate gene expression without DNA nucleotide sequence changes. These processes, physiologically involved in cell differentiation and the maintenance of the differentiated state, also play an important role in the complex interplay between genes and the environment. This interaction may result in the activation or deactivation of genes through induced epigenetic changes, thus facilitating adaptation to different environmental cues. This review provides an overview of the critical role of epigenetic changes in fetal metabolic programming linked to GDM and their long-lasting health consequences.