Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation

Abstract

Maternal nutrition is critically involved in the development and health of the fetus. We evaluated maternal methyl-group donor intake through diet (methionine, betaine, choline, folate) and supplementation (folic acid) before and during pregnancy in relation to global DNA methylation and hydroxymethylation and gene specific (IGF2 DMR, DNMT1, LEP, RXRA) cord blood methylation. A total of 115 mother-infant pairs were enrolled in the MAternal Nutrition and Offspring's Epigenome (MANOE) study. The intake of methylgroup donors was assessed using a food-frequency questionnaire. LC-MS/MS and pyrosequencing were used to measure global and gene specific methylation, respectively. Dietary intake of methyl-groups before and during pregnancy was associated with changes in LEP, DNMT1, and RXRA cord blood methylation. Statistically significant higher cord blood LEP methylation was observed when mothers started folic acid supplementation more than 6 months before conception compared with 3-6 months before conception (34.6 § 6.3% vs. 30.1 § 3.6%, P D 0.011, LEP CpG1) or no folic acid used before conception (16.2 § 4.4% vs. 13.9 § 3%, P D 0.036 for LEP CpG3 and 24.5 § 3.5% vs. 22.2 § 3.5%, P D 0.045 for LEP mean CpG). Taking folic acid supplements during the entire pregnancy resulted in statistically significantly higher cord blood RXRA methylation as compared with stopping supplementation in the second trimester (12.3 § 1.9% vs. 11.1 § 2%, P D 0.008 for RXRA mean CpG). To conclude, long-term folic acid use before and during pregnancy was associated with higher LEP and RXRA cord blood methylation, respectively. To date, pregnant women are advised to take a folic acid supplement of 400 mg/day from 4 weeks before until 12 weeks of pregnancy. Our results suggest significant epigenetic modifications when taking a folic acid supplement beyond the current advice.

Methyl Donor Nutrients in Chronic Kidney Disease: Impact on the Epigenetic Landscape

“…Maintenance of the methylome is critical to the integrity of the epigenome. This is regulated via one carbon metabolism and, thus, in turn by nutritional input of methyl donors, such as Met, folate, vitamin B-12, choline and betaine which are substrate providers for many epigenetic processes (12,13). Little is known about how nutrients affect epigenetic processes in CKD.…”

Supplementing rainbow trout (Oncorhynchus mykiss) broodstock diets with choline and methionine improves growth in offspring

“…Research in mammals has further investigated the effects of maternal nutrition on the offspring epigenome and also determined that maternal imprinting via epigenetic modifications are, in part, responsible for the effects on offspring health and development (Cooper et al, ; El Hajj, Schneider, Lehnen, & Haaf, ; Fowden, Coan, Angiolini, Burton, & Constancia, ; Ivanova, Chen, Segonds‐Pichon, Ozanne, & Kelsey, ; Jousse et al, ). Additional studies have confirmed that the maternal intake of nutrients essential for cellular methylation reactions such as methionine, choline, and folate can alter epigenetic patterns in the offspring (Amarasekera et al, ; Medici et al, ; Pauwels et al, ). Therefore, research in mammals and fish collectively support that epigenetic modifications may be partially responsible for the nutritional programming response observed from methionine and choline supplementation in the current study.…”

Transgenerational Inheritance of Betaine‐Induced Epigenetic Alterations in Estrogen‐Responsive IGF‐2/IGFBP2 Genes in Rat Hippocampus

“…[ 18 ] Previous study reported that maternal intake of methyl donors, including folate, betaine and choline, during different gestation period alters epigenetic modifications of many imprinted genes in the genomic DNA isolated from cord blood. [ 19 ]…”