Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring.

Wen Li,John Wilson,Zhenshu Li,Shou Li,Xinyan Wang,Guowei Huang

doi:10.3390/nu10030292

Abstract

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function.

Highlights

Folate requirements are increased during pregnancy because of the increased abundance of one-carbon transfer reactions for DNA synthesis and methylation reactions [1,2]
A new DNA methylation pattern is established during embryogenesis soon after implantation and the genome and epigenome of the developing fetus may be highly susceptible to environmental modifiers such as maternal folate levels [13]
The rats were randomly assigned to four groups: (1) folate-deficient diet group (DD group) that was fed a folate-deficient diet from seven days before mating to delivery; (2) folic acid normal diet group (ND group) that was fed a control diet from seven days before mating to delivery; (3) folic acid supplementation diet short-period group (FD-S group) that was fed a control diet from seven days before mating to delivery except for a 10-day-long period when this group was fed a folic acid supplementation diet; (4) folic acid supplementation diet long-period group (FD-L group) that was fed a folic acid supplementation diet from seven days before mating to delivery

Summary

Introduction

Folate requirements are increased during pregnancy because of the increased abundance of one-carbon transfer reactions for DNA synthesis and methylation reactions [1,2]. Folic acid supplementation at 400 μg per day or higher is recommended worldwide before and during early stages of pregnancy to reduce the incidence of neural tube defects (NTDs) [3]. The food supply in many countries is fortified with folic acid to increase folate levels in women of childbearing age and thereby decrease NTDs risk [4]. High maternal folate levels may have other beneficial effects in offspring, such as reduced risks of low birth weight, language delay, autism, and childhood brain tumors [5,6,7,8,9]. A new DNA methylation pattern is established during embryogenesis soon after implantation and the genome and epigenome of the developing fetus may be highly susceptible to environmental modifiers such as maternal folate levels [13]

Methods

Results

Conclusion