Epigenetic Modifications at the Center of the Barker Hypothesis and Their Transgenerational Implications

Embryo/fetal nutrition and the environment in the reproductive tract influence the subsequent risk of developing adult diseases and disorders, as formulated in the Barker hypothesis. Metabolic syndrome, obesity, heart disease, and hypertension in adulthood have all been linked to unwanted epigenetic programing in embryos and fetuses. Multiple studies support the conclusion that environmental challenges, such as a maternal low-protein diet, can change one-carbon amino acid metabolism and, thus, alter histone and DNA epigenetic modifications. Since histones influence gene expression and the program of embryo development, these epigenetic changes likely contribute to the risk of adult disease onset not just in the directly affected offspring, but for multiple generations to come. In this paper, we hypothesize that the effects of parental nutritional status on fetal epigenetic programming are transgenerational and warrant further investigation. Numerous studies supporting this hypothesis are reviewed, and potential research techniques to study these transgenerational epigenetic effects are offered.