Paternal folate status at mating influences fetal brain IGF‐2 expression in rats

Abstract

We investigated the effect of paternal folate status on placental and fetal whole brain folate content and DNA methylation, and fetal whole brain insulin‐like growth factor‐2 (IGF‐2) expression in rats. Rats were divided into four groups: paternal folate‐supplemented (PS) or folate‐deficient (PD), and maternal folate‐supplemented (MS) or folate‐deficient (MD) and were fed with folic acid‐supplemented (8mg/kg) and folic acid‐deficient (0mg/kg) diets. After 4 weeks, rats were mated (PS×MS, PS×MD, PD×MS and PD×MD) and placenta and fetal whole brain were isolated at day 20 of gestation. Folate content, DNA methylation and the expression of IGF‐2 in the placenta and brain analyzed by microbiological assay, ELISA and western blot technique, respectively. Compared to the PS×MS group, placental folate content (P < 0.0001) and DNA methylation in placenta (P < 0.0001) and brain (P < 0.0001) was significantly decreased in the PD×MS group as much as the PS×MD group. Brain folate content was decreased in the PD×MS group as much as the level of PD×MD group (P < 0.05). As compared to PS×MS group, the expression of IGF‐2 in the PD×MS group was decreased as much as the level of the PD×MD group (P < 0.0001). These results suggest that the effect of paternal folate deficiency could be as important to the growth and development of placenta and brain of the fetus as maternal folate deficiency.