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

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.