Nutrition, Epigenetics and Complex Birth Defects

Abstract

Birth defects are a global problem that affects ~6% of births worldwide. In the U.S., birth defects are the leading cause of pediatric hospitalizations, medical expenditures, and death in the first year of life. Globally, at least 3.3 million children <5 years die each year because of a birth defect. Indeed, birth defects are one of, if not the leading healthcare concern for the youngest members of society. Neural tube defects (NTDs) are the 2nd most common of all human birth defects, annually affecting approximately 324,000 births worldwide and 3,000 pregnancies in the U.S.We have explored the potential role of environmental factors that alter maternal epigenetic homeostasis and contributes to birth defects. We believe that environmental exposures or nutritional status can impact production of reactive oxidative molecules, the availability of methyl groups, methyltransferase activity, inflammation and endocrine disruption which all have epigenetic implications during the process of neural tube closure. Such exposures may modify multiple biological processes that affect epigenetic mechanisms, including DNA methylation, histone codes, and miRNA expression. These changes may, in turn, modify chromatin organization and condensation, gene expression, and adversely affect pathogenetic processes in the developing embryo. Such factors may interact and act synergistically, such as a nutritional folate deficiency may create altered immune responses that compromise neural tube closure. An in depth exploration of the epigenetic relationship between environmental toxicants, nutritional status and the developmental impact on the embryo will be the focus of this presentation.Supported by NIH grants DE016315 and NS050249