The Effect of Paternal Folic Acid Supplementation on Folate Concentrations and DNA Methylation of Offspring in a Mouse Model

Background: DNA methylation is programmed during embryogenesis, and folate is critical in the one-carbon transfer reactions. Maternal folic acid (FA) supplementation has been shown to significantly modify offspring DNA methylation. However, the role of paternal folate status is unknown. We investigated the effect of paternal FA supplementation on offspring DNA methylation. Methods: Weanling male C57BL/6 mice (n=20) were randomized to 2 or 20 mg FA/kg diets. After 3-4 weeks, breeding began with females on the control diet. At birth, pups were sacrificed, and plasma and tissues collected. Folate concentrations were determined by standard microbiologic assay, and Ppar-a, Ppar-g, Gr and Igf-2 methylation by bisulfite conversion and pyrosequencing. Results: Paternal supplementation significantly decreased the breeding period (pM.Sc.2017-12-07 00:00:0