Effects of parental folate deficiency on the folate content, global DNA methylation, and expressions of FR, IGF-2 and IGF-1R in the postnatal rat liver

We examined the effect of parental folate deficiency on the folate content, global DNA methylation, folate receptor-alpha (FR${\alpha}$), insulin-like-growth factor-2 (IGF-2) and -1 receptor (IGF-1R) in the liver and plasma homocysteine in the postnatal rat. Male and female rats were randomly fed a folic acid-deficient (paternal folate-deficient, PD and maternal folate-deficient, MD), or folic acid-supplemented diet (paternal folate-supplemented, PS and maternal-folate-supplemented, MS) for four weeks. They were mated and grouped accordingly: $PS{\times}MS$, $PS{\times}MD$, $PD{\times}MS$, and $PD{\times}MD$. Pups were killed on day 21 of lactation. The hepatic folate content was markedly reduced in the $PD{\times}MD$ and $PS{\times}MD$ and $PD{\times}MS$ as compared with the $PS{\times}MS$ group. The hepatic global DNA methylation was decreased in the $PD{\times}MS$ and $PS{\times}MD$ groups as much as in the $PD{\times}MD$ group, and all the three groups were significantly lower as compared to the $PS{\times}MS$ group. There were no significant differences in the hepatic FR${\alpha}$, IGF-2 and IGF-1R expressions among the groups. Positive correlations were found between the hepatic folate content and global DNA methylation and protein expressions of FR${\alpha}$, IGF-2 and IGF-1R, whereas an inverse correlation was found between hepatic folate content and plasma homocysteine level in the 3-week-old rat pup. The results of this study show that both paternal and maternal folate deficiency at mating can influence the folate content and global DNA methylation in the postnatal rat liver.