Institute for Human Genetics

    Fetal programming of adult disease

    Epidemiological studies suggest that adverse intrauterine conditions during fetal development can be associated with negative health outcomes later in life, in particular increased rates for many metabolic and cardiovascular diseases. The developmental origins hypothesis proposes that prenatal environmental experiences have long-lasting effects on the setting of metabolic pathways and, thus, influence disease susceptibility in later life. Epigenetic changes induced by environmental factors are thought to stably modulate gene expression, providing a link between early life conditions and susceptibility to complex disease. The prevalence of type 2 diabetes and obesity is increasing in most populations worldwide. In addition to overnutrition and physical inactivity, prenatal factors appear to make a significant contribution to the metabolic disease epidemic. It is well known that the offspring of diabetic and/or obese mothers who are exposed to high concentrations of glucose, free fatty acids and amino acids in utero are at increased lifelong risk of developing metabolic disorders. We study the epigenetic effects of gestational diabetes which affects 3-10% of all pregnancies in developed countries. The MEST gene, which encodes a placental/fetal growth factor and is also important for adult behavior, showed significantly lower methylation levels in children who were exposed to GDM in utero. The observation that MEST is also hypomethylated in adults with morbid obesity, compared with normal-weight individuals supports a role for MEST in the development of obesity.

    El Hajj N, Pliushch G, Schneider E, Dittrich M, Müller T, Korenkov M, Aretz M, Zechner U, Lehnen H, Haaf T. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes.

    Schütte B, El Hajj N, Kuhtz J, Nanda I, Gromoll J, Hahn T, Dittrich M, Schorsch M, Müller T, Haaf T. Broad DNA methylation changes of spermatogenesis, inflammation and immune response-related genes in a subgroup of sperm samples for assisted reproduction. Andrology. 2013 Nov;1(6):822-9.