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

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.

Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

“…Maternal folic acid deficiency is associated with alterations of global DNA methylation and DNMT expression and activity [ 153 ], as well as with several developmental disorders [ 153 , 154 , 155 , 156 ]. Folate supplementation helps decrease abnormal development and regulates DNA methylation [ 157 , 158 ], indicating that DNA methylation plays a role in development. There have been various studies in which the importance of folate and the beneficial effect of folate supplementation on DNA methylation status and fetal development were investigated [ 159 , 160 , 161 , 162 , 163 ].…”

The Stimulation of Neurogenesis Improves the Cognitive Status of Aging Rats Subjected to Gestational and Perinatal Deficiency of B9–12 Vitamins

“…In addition, a deceased status in methyl donors is correlated to accelerated cognitive decline and senescence [29][30][31]. Actually, studies using animal models showed the efficiency of supplementations on plasma and body parameters, attesting to a restoration of healthy conditions for animals initially subjected to various methyl-donor deficiencies [28,[32][33][34]. Nevertheless, at least two questions remain unclear.…”

Maternal Folic Acid Impacts DNA Methylation Profile in Male Rat Offspring Associated With Neurodevelopment and Learning/Memory Abilities

“…Periconceptional folic acid (FA) supplementation not only reduces the incidence of neural tube defects, but also improves cognitive performances in offspring [3,4]. Our previous studies demonstrated that maternal FA supplementation during pregnancy promoted offspring's neurogenesis and synaptogenesis at birth [5], stimulated sensorymotor re ex development in infancy [6,7], and exerted long-term bene cial effects on learning and memory abilities in adolescence and adult in rat offspring [6]. However, the genes or pathways that are epigenetically regulated by FA in neurodevelopment were rarely reported.…”

“…Epigenetic alterations are thought to module gene expression and silencing [10], and its dysregulation may contribute to numerous neurodevelopment disorders [11,12]. Maternal FA supplementation during pregnancy increased offspring's global DNA methylation level in rats [7], and in uenced offspring's repeat element and imprinted gene methylation in human [13]. A meta-analysis included 1988 newborns from two European birth cohorts revealed that maternal plasma folate during pregnancy impacted epigenome-wide DNA methylation in cord blood, and some of the implicated genes had functional relevance to neurodevelopment [4].…”