A crucial role for maternal dietary methyl donor intake in epigenetic programming and fetal growth outcomes

Abstract

The fetal origins of health and disease framework has identified extremes in fetal growth and birth weight as factors associated with the lifelong generation of chronic diseases such as obesity, diabetes, cardiovascular disease, and hypertension. Maternal nutrition plays a critical role in fetal and placental development, in part by providing the methyl groups required to establish the fetus's genome structure and function, notably through DNA methylation. The goal of this narrative review is to describe the role of maternal dietary methyl donor (methionine, folate, and choline) and cofactor (zinc and vitamins B2, B6, and B12) intake in one-carbon metabolism and DNA methylation in the fetus and placenta, as well as their impacts on fetal growth and lifelong health outcomes, with specific examples in animals and humans. Based on the available evidence, it is concluded that intake of different amounts of dietary methyl donors and cofactors during pregnancy may alter fetal growth and development, thus establishing a major link between early environmental exposure and disease development in the offspring later in life.

Early feeding of rainbow trout (Oncorhynchus mykiss) with methionine deficient diet over a two-week period: consequences for liver mitochondria in juveniles

“…Several studies have previously shown that dietary methionine deficiency led to a direct body mass reduction in fish (Belghit et al, 2014;Gao et al, 2019;Mambrini et al, 1999;Séité et al, 2018), but to our knowledge no data are available on the programming impact of methionine deficiency on body mass. However, several previous findings in mammals demonstrated that maternal methyl-group donor nutrition might affect susceptibility to obesity and metabolic syndrome of offspring in adulthood (McGee et al, 2018). Interestingly, we observed that whatever the first feeding of fry, the 2 week challenge of juveniles with the MD diet increased the HSI, and this effect was even stronger in fish from fry fed the MD diet at the first meal.…”

The association of maternal dietary folate intake and folic acid supplementation with small-for-gestational-age births: a cross-sectional study in Northwest China

“…Our study showed that a higher dietary folate intake throughout pregnancy was associated with a higher birth weight Z score and that total folate intake during pregnancy was negatively associated with SGA risks and positively associated with the birth weight Z score. As dietary folate is less stable and has a substantially lower bioavailability than synthetic folic acid (14) , the association of total folate intake during pregnancy with SGA risk in the present study was largely attributed to folic acid supplements. Large-scale cohort studies with more comprehensive information on folate status (dietary folate, folic acid supplements, serum folate, and erythrocyte folate) at multiple time points (before conception, in early pregnancy, in middle pregnancy, and in late pregnancy) are needed to further demonstrate the association of folate intake with intra-uterine growth restriction.…”

“…Currently, the underlying molecular mechanisms whereby folic acid can prevent adverse pregnancy outcomes are poorly understood. It is speculated that epigenetic modifications, especially DNA methylation, may be involved in these processes (14) . Folate is an essential component in the one-carbon metabolism pathway as it can provide methyl groups for a series of biochemical reactions, including DNA methylation.…”

“…It has been reported that SGA is associated with increased neonatal mortality and long-term health problems (13) . The fetal origins of health and disease framework suggests that it is imperative to improve maternal nutritional status and therefore prevent the occurrence of fetal growth restriction (14) . To our knowledge, few studies have investigated the association between maternal dietary folate intake during pregnancy and the risk of SGA births (10) .…”

Modulation of the Epigenome by Nutrition and Xenobiotics during Early Life and across the Life Span: The Key Role of Lifestyle

“…The methylation of CpG islands in a gene's promoter region has been associated to a progressive switching off of the gene, and the availability of methyl groups required for methylation depends on a folate-rich diet (e.g., spinach, green leaves, peas, asparagus, etc.) as well as sufficient levels of B12 and B6 vitamins [2,3]. Deficiencies in these micronutrients during early life have been associated with increased risk of cardiovascular, metabolic, and neurological diseases later in life [4,5].…”