Folate and fetal programming: a play in epigenomics?

Guéant, Jean‐Louis; Namour, Farès; Guéant-Rodríguez, Rosa-María; Daval, Jean‐Luc

doi:10.1016/j.tem.2013.01.010

Cited by 149 publications

(130 citation statements)

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“…Our group previously reported higher levels of insulin-like growth factor 2 (IGF2) DMR methylation in white blood cell DNA from very young children after periconceptional exposure to maternal folic acid supplement use (Steegers-Theunissen et al 2009). This is supported by human and animal studies also emphasizing the importance of the 1-C pathway in fetal programing (Gueant et al 2013.…”

Section: Introductionmentioning

confidence: 63%

Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles

Mil¹,

Bouwland-Both²,

Stolk³

et al. 2014

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Correspondence should be addressed to R P M Steegers-Theunissen; Email: r.steegers@erasmusmc.nl † R P M Steegers-Theunissen is now at Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, The Netherlands AbstractMaternal one-carbon (1-C) metabolism provides methylgroups for fetal development and programing by DNA methylation as one of the underlying epigenetic mechanisms. We aimed to investigate maternal 1-C biomarkers, folic acid supplement use, and MTHFR C677T genotype as determinants of 1-C metabolism in early pregnancy in association with newborn DNA methylation levels of fetal growth and neurodevelopment candidate genes. The participants were 463 mother-child pairs of Dutch national origin from a large populationbased birth cohort in Rotterdam, The Netherlands. In early pregnancy (median 13.0 weeks, 90% range 10.4-17.1), we assessed the maternal folate and homocysteine blood concentrations, folic acid supplement use, and the MTHFR C677T genotype in mothers and newborns. In newborns, DNA methylation was measured in umbilical cord blood white blood cells at 11 regions of the seven genes: NR3C1, DRD4, 5-HTT, IGF2DMR, H19, KCNQ1OT1, and MTHFR. The associations between the 1-C determinants and DNA methylation were examined using linear mixed models. An association was observed between maternal folate deficiency and lower newborn DNA methylation, which attenuated after adjustment for potential confounders. The maternal MTHFR TT genotype was significantly associated with lower DNA methylation. However, maternal homocysteine and folate concentrations, folic acid supplement use, and the MTHFR genotype in the newborn were not associated with newborn DNA methylation. The maternal MTHFR C677T genotype, as a determinant of folate status and 1-C metabolism, is associated with variations in the epigenome of a selection of genes in newborns. Research on the implications of these variations in methylation on gene expression and health is recommended.

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Section: Introductionmentioning

confidence: 63%

Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles

Mil¹,

Bouwland-Both²,

Stolk³

et al. 2014

Reproduction

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“…In agreement with these mechanisms, we observed a reduced expression of PRMT-1 and a decreased SAM/SAH ratio, which led to a decreased methylation of ER-a, a decreased interaction between ER-a and PGC-1a, and an imbalanced detection of ER-a and PGC-1a in the cytoplasm and the nucleus of the deficient cells (30)(31)(32)(33). We have previously observed such a decreased interaction between PGC-1a and nuclear receptors through impaired methylation in the liver and the heart of MDD animals (1,(34)(35)(36). The impaired ER-a pathway led to decreased synapsins through decreased expression of the zinc finger transcriptional factor EGR-1/Zif-268.…”

Section: Discussionmentioning

confidence: 96%

Folate- and vitamin B₁₂–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α

Pourié¹,

Martin²,

Bossenmeyer‐Pourié³

et al. 2015

The FASEB Journal

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Deficiency in the methyl donors vitamin B 12 and folate during pregnancy and postnatal life impairs proper brain development. We studied the consequences of this combined deficiency on cerebellum plasticity in offspring from rat mothers subjected to deficient diet during gestation and lactation and in rat neuroprogenitor cells expressing cerebellum markers. The major proteomic change in cerebellum of 21-d-old deprived females was a 2.2-fold lower expression of synapsins, which was confirmed in neuroprogenitors cultivated in the deficient condition. A pathway analysis suggested that these proteomic changes were related to estrogen receptor a (ER-a)/Src tyrosine kinase. The influence of impaired ER-a pathway was confirmed by abnormal negative geotaxis test at d 19-20 and decreased phsophorylation of synapsins in deprived females treated by ER-a antagonist 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP). This effect was consistent with 2-fold decreased expression and methylation of ER-a and subsequent decreased ER-a/PPAR-g coactivator 1 a (PGC-1a) interaction in deficiency condition. The impaired ER-a pathway led to decreased expression of synapsins through 2-fold decreased EGR-1/Zif-268 transcription factor and to 1.7-fold reduced Src-dependent phosphorylation of synapsins. The treatment of neuroprogenitors with either MPP or PP1 (4-(49-phenoxyanilino)-6,7-dimethoxyquinazoline, 6,7-dimethoxy-N-(4-phenoxyphenyl)-4-quinazolinamine, SKI-1, Src-l1) Src inhibitor produced similar effects. In conclusion, the deficiency during pregnancy and lactation impairs the expression of synapsins through a deregulation of ER-a pathway.-Pourié, G., Martin, N., Bossenmeyer-Pourié, C., Akchiche, N., Guéant-Rodriguez, R. M., Geoffroy, A., Jeannesson, E., El Hajj Chehadeh, S., Mimoun, K., Brachet, P., Koziel, V., Alberto, J.-M., Helle, D., Debard, R., Leininger, B., Daval, J.-L., Guéant, J.-L. Folate-and vitamin B 12 -deficient diet during gestation and lactation alters cerebellar synapsin expression via impaired influence of estrogen nuclear receptor a. FASEB J. 29, 3713-3725 (2015). www.fasebj.org

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“…Folate, vitamin B12 and choline are methyl donors and involved in the synthesis of methionine, the precursor of the universal donor of methyl groups needed for DNA methylation (S-adenosylmethionine). As a result, dysregulation in any of these components can alter the epigenomic regulation of gene expression [240]. With respect to postnatal determinants of DNA methylation, exercise interventions have been shown to alter the DNA methylation of 2817 genes in skeletal muscle and 7663 genes in adipose tissue (18 of which were obesity candidate genes) [241].…”

Section: Biological Processes Underlying Statistical Gene-environmentmentioning

confidence: 99%

The importance of gene–environment interactions in human obesity

2016

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The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene-environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene-environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations.

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Folate and fetal programming: a play in epigenomics?

Cited by 149 publications

References 120 publications

Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles

Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles

Folate- and vitamin B₁₂–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α

The importance of gene–environment interactions in human obesity

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Folate and fetal programming: a play in epigenomics?

Cited by 149 publications

References 120 publications

Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles

Determinants of maternal pregnancy one-carbon metabolism and newborn human DNA methylation profiles

Folate- and vitamin B12–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α

The importance of gene–environment interactions in human obesity

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Folate- and vitamin B₁₂–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α