Effects of paternal folate deficiency on the expression of insulin-like growth factor-2 and global DNA methylation in the fetal brain.

SCOPE: We examined the effect of paternal folate deficiency on the folate content, the percentage of 5-methycytosine (percentage of 5-mC) in the total DNA, and the protein expression of insulin-like growth factor-2 (IGF-2) in the fetal whole brain. METHODS AND RESULTS: Rats were mated after males were fed a folic acid deficient (PD) or folic acid supplemented (PS) diet for 4 weeks, and fetuses were killed on day 20 of gestation. The folate content in the fetal liver was significantly lower in the PD group than in the PS group, whereas it did not differ in the fetal whole brain. The percentage of 5-mC and the protein expression of IGF-2 in the fetal whole brain were both lower in the PD group than in the PS group. There were positive correlations between paternal liver and testis folate content and the percentage of 5-mC and IGF-2 expression in the fetal whole brain. CONCLUSION: Our results on the folate content, the percentage of 5-mC, and IGF-2 expression in the fetal whole brain show that paternal folate deficiency at mating can influence fetal brain DNA methylation and IGF-2 expression despite an adequate maternal folate status during the gestational period.