High dietary folate and low vitamin B12 in parental diet disturbs the epigenetics of imprinted genes MEST and PHLDA2 in mice placenta

Abstract

To elucidate the dietary effects of vitamin B12 and folic acid on fetal and placental epigenetics, different dietary combinations of folic acid and low vitamin B12 (four groups) were fed to the animals (C57BL/6 mice), and mating was carried out within each group in the F0 generation. After weaning for 3 weeks in the F1 generation each group is divided into two sub-groups, while one group of mice was continued on the same diet (sustained group), the other was shifted to a normal diet (transient group) for 6–8 weeks (F1). Mating was carried out again within each group, and on day 20 of gestation, the maternal placenta (F1) and fetal tissues (F2) were isolated. Expression of imprinted genes and various epigenetic mechanisms, including global and gene-specific DNA methylation and post-translational histone modifications, were studied. Evaluation of mRNA levels of MEST and PHLDA2 in placental tissue revealed that their expression is maximally influenced by vitamin B12 deficiency and high folate conditions. The gene expression of MEST and PHLDA2 was found significantly decreased in the F0 generation, while over-expression was seen in BDFO dietary groups of F1 generation. These dietary combinations also resulted in DNA methylation changes in both generations, which may not play a role in gene expression regulation. However, altered histone modifications were found to be the major regulatory factor in controlling the expression of genes in the F1 generation. The imbalance of low vitamin B12 and high folate leads to increased levels of activating histone marks, contributing to increased gene expression.