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Nutrients 2016, 8(10), 661;

Organ-Specific Gene Expression Changes in the Fetal Liver and Placenta in Response to Maternal Folate Depletion

Human Nutrition Research Centre, Institute for Health & Society, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK
Human Nutrition Research Centre; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
Maastricht Centre for Systems Biology, MaCSBio, Maastricht University, Maastricht 6200 MD, The Netherlands
Department of Bioinformatics, BiGCaT, Maastricht University, Maastricht 6200 MD, The Netherlands
Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, UK
Author to whom correspondence should be addressed.
Received: 22 August 2016 / Revised: 13 October 2016 / Accepted: 14 October 2016 / Published: 22 October 2016
(This article belongs to the Special Issue B-Vitamins and One-Carbon Metabolism)
PDF [466 KB, uploaded 22 October 2016]


Growing evidence supports the hypothesis that the in utero environment can have profound implications for fetal development and later life offspring health. Current theory suggests conditions experienced in utero prepare, or “programme”, the fetus for its anticipated post-natal environment. The mechanisms responsible for these programming events are poorly understood but are likely to involve gene expression changes. Folate is essential for normal fetal development and inadequate maternal folate supply during pregnancy has long term adverse effects for offspring. We tested the hypothesis that folate depletion during pregnancy alters offspring programming through altered gene expression. Female C57BL/6J mice were fed diets containing 2 mg or 0.4 mg folic acid/kg for 4 weeks before mating and throughout pregnancy. At 17.5 day gestation, genome-wide gene expression was measured in male fetal livers and placentas. In the fetal liver, 989 genes were expressed differentially (555 up-regulated, 434 down-regulated) in response to maternal folate depletion, with 460 genes expressed differentially (250 up-regulated, 255 down-regulated) in the placenta. Only 25 differentially expressed genes were common between organs. Maternal folate intake during pregnancy influences fetal gene expression in a highly organ specific manner which may reflect organ-specific functions. View Full-Text
Keywords: transcriptome; programming; developmental origins of health and disease; pregnancy; diet transcriptome; programming; developmental origins of health and disease; pregnancy; diet

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McKay, J.A.; Xie, L.; Adriaens, M.; Evelo, C.T.; Ford, D.; Mathers, J.C. Organ-Specific Gene Expression Changes in the Fetal Liver and Placenta in Response to Maternal Folate Depletion. Nutrients 2016, 8, 661.

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