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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #306926
Title: Maternal nutrition at conception modulates DNA methylation of human metastable epialleles

Author
item DOMINGUEZ-SALAS, PAULA - London School Of Hygiene & Tropical Medicine
item MOORE, SOPHIE - London School Of Hygiene & Tropical Medicine
item BAKER, MARIA - Children'S Nutrition Research Center (CNRC)
item BERGEN, ANDREW - Sri International
item COX, SHARON - London School Of Hygiene & Tropical Medicine
item DYER, ROGER - University Of British Columbia
item FULFORD, ANTHONY - London School Of Hygiene & Tropical Medicine
item GUAN, YONGTAO - Children'S Nutrition Research Center (CNRC)
item LARITSKY, ELEONORA - Children'S Nutrition Research Center (CNRC)
item SILVER, MATT - London School Of Hygiene & Tropical Medicine
item SWAN, GARY - Stanford University School Of Medicine
item ZEISEL, STEVEN - University Of North Carolina
item INNIS, SHEILA - University Of British Columbia
item WATERLAND, ROBERT - Children'S Nutrition Research Center (CNRC)
item PRENTICE, ANDREW - London School Of Hygiene & Tropical Medicine
item HENNIG, BRANWEN - London School Of Hygiene & Tropical Medicine

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/26/2014
Publication Date: 4/29/2014
Citation: Dominguez-Salas, P., Moore, S.E., Baker, M.S., Bergen, A.W., Cox, S.E., Dyer, R.A., Fulford, A.J., Guan, Y., Laritsky, E., Silver, M.J., Swan, G.E., Zeisel, S.H., Innis, S.M., Waterland, R.A., Prentice, A.M., Hennig, B.J. 2014. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nature Communications. 5:3746.

Interpretive Summary: In experimental animals, maternal diet around the time of conception influences the establishment of DNA methylation at specific genomic regions called metastable epialleles in the offspring, causing permanent changes in outcomes including coat color and propensity for obesity. Pronounced naturally-occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We showed that significant seasonal variations in dietary intake of mothers around the time of conception, with consequent effects on maternal nutritional status, predict methylation patterns that are strongly correlated in DNA extracted from different cell types in the infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic (i.e. cross-tissue) epigenetic changes in humans. These findings provide an important step toward understanding how maternal nutrition before and during pregnancy can affect lifelong health of her child.

Technical Abstract: In experimental animals, maternal diet during the periconceptional period influences the establishment of DNA methylation at metastable epialleles in the offspring, with permanent phenotypic consequences. Pronounced naturally occurring seasonal differences in the diet of rural Gambian women allowed us to test this in humans. We show that significant seasonal variations in methyl-donor nutrient intake of mothers around the time of conception influence 13 relevant plasma biomarkers. The level of several of these maternal biomarkers predicts increased/decreased methylation at metastable epialleles in DNA extracted from lymphocytes and hair follicles in infants postnatally. Our results demonstrate that maternal nutritional status during early pregnancy causes persistent and systemic epigenetic changes at human metastable epialleles.