Maternal obesity, diabetes during pregnancy and epigenetic mechanisms that influence the developmental origins of cardiometabolic disease in the offspring

Since 1980, global obesity has doubled, and the incidence of cardiometabolic diseases such as type 2 diabetes and heart disease is also increasing. While genetic susceptibility and adult lifestyle are implicated in these trends, evidence from clinical cohorts, epidemiological studies and animal model experiments support a role for early-life environmental exposures in determining the long-term health of an individual, which has led to the formulation of the Developmental Origins of Health and Disease (DOHaD) theory. In fact, maternal obesity and diabetes during pregnancy, which are on the rise, are strongly associated with altered fetal growth and development as well as with lifelong perturbations in metabolic tissues. A mounting body of evidence implicates epigenetic mechanisms (e.g. DNA methylation and histone modifications) in the regulation of these effects and their transmission to future generations. This review critically discusses the current evidence (in animal model systems and humans) that implicates maternal obesity and diabetes during pregnancy in perturbing the epigenome of the next generation, and the consequential impact on growth, organ development and ultimately cardiometabolic disease progression. Additionally, this review will address some of the limitations of the DOHaD approach and areas that require further study. For example, future research requires verification of the mechanistic impact of the epigenetic marks and their persistence over the life course. Ultimately, this knowledge is needed to establish optimal screening, prevention and therapeutic approaches for children at risk of cardiometabolic disease development.