Epigenetic processes in transmission of prenatally-induced phenotypes between generations

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Babies born to mothers who have poor nutrition during pregnancy have an increased risk of heart attack, stroke, high blood pressure, type 2 diabetes mellitus and obesity when they become adults. There is emerging evidence that the consequences of such nutrition during pregnancy can be passed to grandchildren even when their daughters have adequate nutrition during pregnancy. These effects have been replicated in the offspring of rats fed a diet with reduced protein content during pregnancy. We have identified a mechanism by which poor nutrition during pregnancy can result in changes to how genes are controlled in the fetus and give which result in increased risk of disease in a future generation. This process of gene control is called epigenetics. In this project we will use the rat model to investigate the mechanism by which the diet of the mother changes the epigenetic control of genes in the next three generations of offspring. We already have evidence that this involves an enzyme called DNA methyltransferase-1 in the first generation and now we need to determine whether this enzyme is involved in subsequent generations. We have also shown adding folic acid to the mother's diet prevents changes in the epigenetic control of genes in the first generations. We will investigate whether folic acid can prevent changes in epigenetic control in successive generations.