Epigenetics and Fetal Metabolic Programming: A Call for Integrated Research on Larger Cohorts

Abstract

Fetal metabolic programming is a concept first suggested by Barker and Hales (1,2) in the early 1990s. On the basis of compelling epidemiological evidence, they hypothesized that fetal and perinatal events, such as maternal undernutrition, were central to determine one’s risk to develop chronic metabolic diseases. Such conditions, including obesity, diabetes, and cardiovascular diseases, have become a very important population health concern. Since the first introduction of this concept, it has been corroborated by many animal but only few human studies (3). Therefore, a number of key issues remain to be clarified, with the most important being our knowledge of the mechanisms involved in fetal metabolic programming. In brief, more research is needed in human models of fetal metabolic programming. One such promising model is gestational diabetes mellitus (GDM). GDM is a form of diabetes first diagnosed during pregnancy. It is the most important cause of hyperglycemia in the course of pregnancy, and its prevalence ranges from 1 to 20% (4). Regrettably, its occurrence is predicted to grow rapidly in the next years as obesity and diabetes are significant risk factors for this condition (5). In other words, GDM is prevalent, increasingly common, and predicts the development of diabetes in mothers. Maybe more importantly, GDM is also associated with a two- to fourfold increased risk for offspring to develop overweight/obesity and the metabolic syndrome, respectively (3). GDM is thus an important health issue considering that glucose metabolism impairments might arise in children as young as 3 years …