Maternal folic acid supplementation alters gene expression in the offspring brain

Studies have indicated that altered maternal micronutrients and vitamins influence the development and susceptibility of newborns to chronic diseases. Among these, folic acid (FA) plays a key role in the synthesis and repair of DNA, along with maintenance of epigenetic DNA methylation. Deficiency of FA has been associated with the pathogenesis of neural tube defects. Since FA can modulate DNA methylation and affect gene expression, we investigated the effect of gestational FA supplementation on the expression of genes in the offspring brain. Our results suggest that a maternal ten-fold increase in FA supplementation alters the expression and dysregulates a number of genes in the offspring brain, including many involved in development. While a number of genes that were dysregulated were common to both male and female pups, there were sex differences in gene expression changes. C57BL/6J female mice were separated into two groups of ten mice and supplemented with a custom diet. One week prior to mating the low-dose group of female mice were fed a custom AIN-93G amino acid–based diet (Research Diet, Inc. New-Brunswick, NJ), with FA at 0.4 mg/kg, while the high-dose group received FA at 4 mg/kg diet. Tissues from the cerebral hemisphere of three independent pups of same gender were pooled together. A total of three microarray gene expression studies have been performed (0.4mg/kg or 4mg/kg both male and female) and the mean was used for comparison.