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      Nutrition During Pregnancy Impacts Offspring’s Epigenetic Status—Evidence from Human and Animal Studies

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          Abstract

          Pregnancy is a vital time of growth and development during which maternal nutrition significantly influences the future health of both mother and baby. During pregnancy, the fetus experiences a critical period of plasticity. Epigenetics, specifically DNA methylation, plays an important role here. As nutrition is influential for DNA methylation, this review aims to determine if maternal nutrition during pregnancy can modify the offspring’s epigenome at birth. Research focuses on micronutrients and methyl donors such as folate and B vitamins. Evidence suggests that maternal nutrition does not largely influence global methylation patterns, particularly in nutrient-replete populations; however, an important impact on gene-specific methylation is observed. A link is shown between maternal nutrition and the methylome of the offspring; however, there remains a paucity of research. With the potential to use DNA methylation patterns at birth to predict health of the child in later life, it is vital that further research be carried out.

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          Most cited references34

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          Fetal origins of coronary heart disease.

          The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease. Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological, and structural parameters. Studies in humans have shown that men and women whose birth weights were at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations. The programming of blood pressure, insulin responses to glucose, cholesterol metabolism, blood coagulation, and hormonal settings are all areas of active research.
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            DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status.

            A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B(12) and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes.
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              Fetal programming and adult health.

              Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of 'programming', whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may result from adaptations invoked when the materno-placental nutrient supply fails to match the fetal nutrient demand. Although the influences that impair fetal development and programme adult cardiovascular disease remain to be defined, there are strong pointers to the importance of maternal body composition and dietary balance during pregnancy.
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                Author and article information

                Journal
                Nutr Metab Insights
                Nutr Metab Insights
                Nutrition and Metabolic Insights
                Nutrition and Metabolic Insights
                Libertas Academica
                1178-6388
                2015
                16 February 2016
                : 8
                : Suppl 1
                : 41-47
                Affiliations
                [1 ]Department of Obstetrics & Gynaecology, School of Medicine and Medical Science, National Maternity Hospital, University College Dublin, Dublin, Ireland.
                [2 ]UCD Institute of Food and Health, University College Dublin, Dublin, Ireland.
                Author notes
                Article
                nmi-suppl.1-2015-041
                10.4137/NMI.S29527
                4758803
                26917970
                33dd3630-6fe9-4df2-a350-d1c198894120
                © 2015 the author(s), publisher and licensee Libertas Academica Ltd.

                This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.

                History
                : 12 October 2015
                : 19 January 2016
                : 21 January 2016
                Categories
                Review

                epigenetics,pregnancy,nutrition,programing,offspring
                epigenetics, pregnancy, nutrition, programing, offspring

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