Maternal folate and DNA methylation in offspring

Abstract

Folate plays a critical role in DNA methylation as it is a key source of methyl donors via the one-carbon metabolism cycle. Folate supplementation is recommended during the periconceptional period for the prevention of neural tube defects in offspring. However, maternal folate levels during pregnancy may also influence the risk of many other conditions in offspring, but the underlying mechanisms involved are unclear. As such, it is important to investigate the possible association between maternal folate status and disease risk that act via modulation of the methylome. Improving methods and technologies available for profiling DNA methylation has allowed for rapidly expanding investigations in this field; however, limitations in study design remain. On the available evidence, global DNA methylation does not appear to be associated with maternal folate status in cord blood samples, but this response may be tissue specific as correlations have been found in fetal brains and adult murine intestines. Several studies have shown differential locus-specific methylation in response to maternal folate status. However, results may vary depending on the assay methods employed, including different assessments of the methylome, different measures of folate status, and cohort composition. Although maternal folate status is linked to disease risk, additional research is required to link this modulation of the methylome to altered health and disease outcomes.