Epigenetic regulation of gene expression as a mechanism of nutritional programming and developmental origins of health and disease

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The diet of an individual has important health issues at any stage of life - 'we are what we eat' after all. However, there is evidence to suggest that the diet of a pregnant woman is particularly important as it has major long-term implications on the health of her offspring - so, in some ways 'we also are what our mothers ate during pregnancy'. Normal term babies born from mothers with poor nutrition during pregnancy usually have a low weight. It has been shown that individuals with a low birth weight are not only less likely to survive delivery but are also at substantially increased risk of developing various common diseases such as diabetes, hypertension and heart disease in adulthood. The underlying causes of the relationship between poor early growth and disease in adulthood are not known, but we believe that the quality of the diet of women during pregnancy is critically important. Many of our attempts to decipher mechanisms of human diseases both rely and benefit from studying animal models. We have shown in a rodent model that if pregnant animals have too little protein during pregnancy their babies are small at birth and develop diabetes in adulthood. We have identified important genes in the pancreas that are expressed at low levels in the offspring of protein-restricted mothers compared to control animals. We now plan further to study these animals to understand how a restricted diet is able to perturb expression of key genes involved in pathogenesis of diabetes. We are particularly interested in studying epigenetic mechanisms - that is mechanisms able to change activity of a gene without altering its DNA sequence - that could be triggered by nutritional changes during pregnancy. We also want to know more precisely at which time/s during pregnancy the quality of the mother's diet is most important for giving birth to healthy babies. This will enable us to both identify at risk individuals and to develop intervention strategies to improve the health of both the pregnant women and their offspring.