DMMC Course: EPIGENETICS: FROM MECHANISMS TO MEDICINES

1200-1250 Tuesday 26 June 2007. O’Reilly Hall, University College Dublin.

Endocrine Active Compounds and the Fetal Epigenome
Dr Dana Dolinoy (Duke University Medical Center, USA)

The ability of environmental factors to shape health and disease involves epigenetic mechanisms that mediate gene-environment interactions. To study environmental influences on the fetal epigenome, we utilized the viable yellow agouti (Avy) mouse, in which coat color variation is correlated to epigenetic marks established early in development. Maternal dietary supplementation with genistein, the major phytoestrogen in soy, shifted the coat color of Avy/a offspring toward pseudoagouti (brown) by increasing Avy methylation. Hypermethylation persisted into adulthood and protected offspring from obesity. Second, maternal dietary exposure to bisphenol A (BPA), an estrogenic monomer used in the manufacture of polycarbonate plastic, shifted the coat color of Avy/a offspring toward yellow by decreasing Avy methylation. In both studies, Avy methylation was similar in tissues from the three germ layers, indicating that genistein and BPA act early in development. Maternal nutritional supplementation of the BPA diet counteracted the hypomethylation showing that simple dietary changes can protect against the deleterious effects of environmental toxicants on the fetal epigenome.