Dietary and supplemental maternal methyl-group donor intake and cord blood DNA methylation.
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 methyl-group 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 = 0.011, LEP CpG1) or no folic acid used before conception (16.2 ± 4.4% vs. 13.9 ± 3%, P = 0.036 for LEP CpG3 and 24.5 ± 3.5% vs. 22.2 ± 3.5%, P = 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 = 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 µg/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.
a KU Leuven - University of Leuven , Department of Public Health and Primary Care , Environment and Health , Leuven , Belgium.|b Flemish Institute of Technological Research (VITO), Unit Environmental Risk and Health , Mol , Belgium.
Sara
S
Pauwels
a KU Leuven - University of Leuven , Department of Public Health and Primary Care , Environment and Health , Leuven , Belgium.
Manosij
M
Ghosh
a KU Leuven - University of Leuven , Department of Public Health and Primary Care , Environment and Health , Leuven , Belgium.
Radu Corneliu
RC
Duca
c KU Leuven - University of Leuven , Department of Imaging & Pathology , Leuven , Belgium.|d KU Leuven - University of Leuven, University Hospitals Leuven , Department of Forensic Medicine , Laboratory of Forensic Genetics and Molecular Archeology , Leuven , Belgium.
Bram
B
Bekaert
e KU Leuven - University of Leuven, Center for Molecular and Vascular Biology , Leuven , Belgium.
Kathleen
K
Freson
f International Agency for Research on Cancer, Dietary Exposure Assessment Group , Lyon , France.
Inge
I
Huybrechts
b Flemish Institute of Technological Research (VITO), Unit Environmental Risk and Health , Mol , Belgium.|g Hasselt University, Faculty of Sciences , Diepenbeek , Belgium.
Sabine
S
A S Langie
b Flemish Institute of Technological Research (VITO), Unit Environmental Risk and Health , Mol , Belgium.
Gudrun
G
Koppen
h KU Leuven - University of Leuven , Department of Development and Regeneration , Leuven , Belgium.|i University Hospitals of Leuven , Department of Obstetrics and Gynecology , Leuven , Belgium.
Roland
R
Devlieger
a KU Leuven - University of Leuven , Department of Public Health and Primary Care , Environment and Health , Leuven , Belgium.|j IDEWE, External Service for Prevention and Protection at Work , Heverlee , Belgium.
Lode
L
Godderis
D000328:Adult; D001622:Betaine / Q000008:administration & dosage* / Q000494:pharmacology; D002794:Choline / Q000008:administration & dosage* / Q000494:pharmacology; D015331:Cohort Studies; D019175:DNA Methylation; D004032:Diet; D019587:Dietary Supplements; D057890:Epigenomics; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism*; D005492:Folic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D008715:Methionine / Q000008:administration & dosage* / Q000494:pharmacology; D009749:Nutrition Surveys; D011247:Pregnancy; D011795:Surveys and Questionnaires
D001622:Betaine; D005492:Folic Acid; D008715:Methionine; D002794:Choline
DNA methylation; DNMT1; IGF2; LEP; RXRA; folic acid supplementation; methyl donors; preconception; pregnancy