Author(s): Subit Barua [*] aff1 , Mohammed A Junaid aff1
DNA methylation; epigenetics; lifestyle; pregnancy
Growing evidence suggests that maternal exposure to certain environmental conditions during pregnancy can have significant effects on the growth of the fetus and on susceptibility to chronic diseases later in life. Perhaps, it has been best postulated by Barker [1,2 ] that different windows of gestational development have different effects, depending on the sensitivity and critical windows for specific organs. Etiologically, factors such as different environmental conditions may modulate the developmental origin of adult disease. Epigenetic alterations of the fetal genome during specific windows of gestational development are emerging as one of the hidden mechanisms for such effects beyond the underlying changes in DNA sequences. In addition to individual genetic information, a few among the many factors that can alter offspring's epigenome and thereby modulate disease risk include maternal lifestyle, diet, obesity and exposure to smoking, alcohol or endocrine disruptors. Whereas the hypothesis of the developmental origins of health and disease proposes that environmentally induced changes during early life, including those at conception or fetal life, impact long-term health, emerging studies are linking such onset of diseases with epigenetic alterations [3,4,5,6 ]. It is crucial to understand the impact of such changes in utero , because of the presence of various environmental factors that the fetus experiences during vulnerable periods of development. In this article, we review the link between maternal lifestyle, dietary factors and consumption or exposure to various other environmental factors during gestation and the modulation of the offspring's epigenome. This perspective will include studies from both experimental animal models and human epidemiological studies that will provide some insights into the underlying epigenetic mechanisms.
Recent evidence from observational and experimental studies suggests that maternal nutrition during the gestational period can modulate developmental programming and alter the physiology of the offspring. Such observations are supported by findings from several studies on human cohorts and animal models. These studies have shown that a maternal methyl diet, specifically one that is high in folic acid, during pregnancy can modulate physiological outcomes, including neural tube defects, intrauterine growth restrictions, septal defects, autism spectrum disorder, congenital heart defects, oral clefts, allergy and cancer [7,8,9,10,11,12,13,14 ]. Moreover, maternal diet can induce persistent changes of the offspring genome/epigenome that may result in predisposition to potential disease and risk in adult life [15,16 ]. During pregnancy, the availability of common methyl donors such as folate, choline, serine, betaine and methionine from dietary sources can modulate the synthesis of the central methyl donor, S-adenosyl-methionine and thus alter the DNA methylation and histone modifications in the fetal epigenome, resulting in changes in gene expression. A study in a mouse model showed that methyl supplementation prior to and during pregnancy induced epigenetic changes with a gain in methylation in the agouti long terminal repeat, and thus changes the phenotype and longevity of the offspring [17 ]. A diet rich in methyl donors during pregnancy was also found to induce hypermethylation at the CpG site...