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Maternal Folate, Methyl Donors, One-Carbon Metabolism, Vitamin B12 and Choline in Foetal Programming

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Diet, Nutrition, and Fetal Programming

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Abstract

Experimental and human population studies have established links between the deficit in dietary methyl donors (MDD) of one-carbon metabolism (1-CM) during pregnancy and foetal programming. This review on MDD foetal programming is focused on the mechanisms dissected in animal models and the associations with outcomes of obesity, metabolic syndrome and cognition in population studies. 1-CM plays a central role in the influence of metabolic and nutritional factors on DNA methylation and regulation of gene expression through its role on the synthesis of S-adenosylmethionine (SAM), which is needed for methylation of DNA, RNA and histones, the activation of nuclear receptor pathways and the adaptation to cellular stress. This complex metabolic network is regulated by a number of genes and requires micronutrients such as folate, vitamins B12 and B6 and choline to function properly. Experimental and epidemiological studies have clearly demonstrated an association between dietary and metabolic markers of the 1-CM and birth weight and age-related manifestations of foetal programming, including neurodevelopment and cognition, in which epigenomic mechanisms may play a central role. Some of the MDD foetal programming effects are exerted by altered methylation of differentially methylated region (DMR) and imprinted genes. These associations illustrate the need to perform further integrated analyses associating epigenomic and transcriptomic analyses and metabolic and nutritional factors that influence the outcomes of MDD foetal programming.

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Abbreviations

MTHFD1, MTHFD2:

Methylenetetrahydrofolate dehydrogenase 1 and 2

1-CM:

One-carbon metabolisms

AHCY:

Adenosylhomocysteinase

BHMT:

Betaine homocysteine methyltransferase

BMI:

Body mass index

CBS:

Cystathionine beta-synthase

CTH:

Cystathionine gamma-lyase

DHFR:

Dihydrofolate reductase

DMR:

Differentially methylated region

DOHaD:

Developmental origins of health and disease

ER-α:

Oestrogen receptor alpha

ERR-α:

Oestrogen-related receptor alpha

EWAS:

Epigenome wide association studies

HAT:

Histone acetyltransferase

HDAC:

Histone deacetylase

HDM:

Histone demethylase

HIF-1α:

Hypoxia-inducible factor

HMT:

Histone methyltransferase

HNF-4:

Hepatic nuclear factor 4

HOMA-IR:

Homeostasis model assessment of insulin resistance

HSF1:

Heat shock factor protein 1

IGF1:

Insulin-like growth factor 1

IUGR:

Intrauterine growth restriction

MDD:

Methyl donor deficiency

MTHFD:

Methylenetetrahydrofolate dehydrogenase

MTHFR:

Methylenetetrahydrofolate reductase

MTR:

Methionine synthase

NASH:

Non-alcoholic steatohepatitis

PGC-1α:

Peroxisome proliferator-activated receptor γ coactivator1α

PPAR-α:

Peroxisome proliferator-activated receptor alpha

PRMT1:

Protein arginine methyltransferase 1

SAH:

S-adenosylhomocysteine

SAM:

S-adenosylmethionine

SHMT:

Serine hydroxymethyltransferase

SIRT:

Sirtuins

TYMS:

Thymidylate synthase

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Acknowledgements

Institutional grants were received from the French national institute for medical research (Inserm), the French national agency for research (ANR Nutrivigene project) and the Region of Lorraine (France). The authors declare no competing financial interests.

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  1. University Hospital Nancy and Inserm 954 Research Unity, N-GERE, (Nutrition-Genetics-Environmental Risks), Institute of Medical Research (Pôle BMS), University of Lorraine, Vandoeuvre les Nancy, France

    Jean-Louis Guéant MD, DSc & Rosa-Maria Guéant-Rodriguez MD, PhD

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  1. Jean-Louis Guéant MD, DSc
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Correspondence to Jean-Louis Guéant MD, DSc .

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  1. Department of Nutrition, King's College, London, United Kingdom

    Rajkumar Rajendram

  2. Department of Nutrition, King's College, London, United Kingdom

    Victor R. Preedy

  3. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Guéant, JL., Guéant-Rodriguez, RM. (2017). Maternal Folate, Methyl Donors, One-Carbon Metabolism, Vitamin B12 and Choline in Foetal Programming. In: Rajendram, R., Preedy, V., Patel, V. (eds) Diet, Nutrition, and Fetal Programming. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-319-60289-9_22

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