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Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.

ABSTRACT: Early-life exposures are critical in fetal programming and may influence function and health in later life. Adequate maternal folate consumption during pregnancy is essential for healthy fetal development and long-term offspring health. The mechanisms underlying fetal programming are poorly understood, but are likely to involve gene regulation. Epigenetic marks, including DNA methylation, regulate gene expression and are modifiable by folate supply. We observed transcriptional changes in fetal liver in response to maternal folate depletion and hypothesized that these changes are concomitant with altered gene promoter methylation.Female C57BL/6J mice were fed diets containing 2 or 0.4?mg folic acid/kg for 4?wk before mating and throughout pregnancy. At 17.5-day gestation, genome-wide gene expression and promoter methylation were measured by microarray analysis in male fetal livers. While 989 genes were differentially expressed, 333 promoters had altered methylation (247 hypermethylated, 86 hypomethylated) in response to maternal folate depletion. Only 16 genes had both expression and methylation changes. However, most methylation changes occurred in genomic regions neighboring expression changes.In response to maternal folate depletion, altered expression at the mRNA level was not associated with altered promoter methylation of the same gene in fetal liver.

SUBMITTER: McKay JA

PROVIDER: S-EPMC5031189 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.

McKay Jill A JA Adriaens Michiel M Evelo Chris T CT Ford Dianne D Mathers John C JC

Molecular nutrition & food research 20160606 9

<h4>Scope</h4>Early-life exposures are critical in fetal programming and may influence function and health in later life. Adequate maternal folate consumption during pregnancy is essential for healthy fetal development and long-term offspring health. The mechanisms underlying fetal programming are poorly understood, but are likely to involve gene regulation. Epigenetic marks, including DNA methylation, regulate gene expression and are modifiable by folate supply. We observed transcriptional chan ...[more]

PMID: 27133805

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Project description:Pregnancy in kidney disease is considered high risk, but the degree of this risk is unclear. We tested the hypothesis that kidney disease in pregnancy is associated with adverse maternal and fetal outcomes.Retrospective study comparing pregnant women with and without kidney disease.Using data from an integrated health care delivery system from 2000 through 2013, a total of 778 women met the criteria for kidney disease. Using a pool of 74,105 women without kidney disease, we selected 778 women to use for matches for the women with kidney disease. These women were matched 1:1 by age, race, and history of diabetes, chronic hypertension, liver disease, and connective tissue disease.Kidney disease was defined using the NKF-KDOQI definition for chronic kidney disease or International Classification of Diseases, Ninth Revision codes prior to pregnancy or serum creatinine level > 1.2mg/dL and/or proteinuria in the first trimester.Maternal outcomes included preterm delivery, delivery by cesarean section, preeclampsia/eclampsia, length of stay at hospital (>3 days), and maternal death. Fetal outcomes included low birth weight (weight < 2,500g), small for gestational age, number of admissions to neonatal intensive care unit, and infant death.Compared with women without kidney disease, those with kidney disease had 52% increased odds of preterm delivery (OR, 1.52; 95% CI, 1.16-1.99) and 33% increased odds of delivery by cesarean section (OR, 1.33; 95% CI, 1.06-1.66). Infants born to women with kidney disease had 71% increased odds of admission to the neonatal intensive care unit or infant death compared with infants born to women without kidney disease (OR, 1.71; 95% CI, 1.17-2.51). Kidney disease also was associated with 2-fold increased odds of low birth weight (OR, 2.38; 95% CI, 1.64-3.44). Kidney disease was not associated with increased risk of maternal death.Data for level of kidney function and cause of death not available.Kidney disease in pregnancy is associated independently with adverse maternal and fetal outcomes when other comorbid conditions are controlled by matching.

Dataset Information

Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.

Publications

Gene promoter DNA methylation patterns have a limited role in orchestrating transcriptional changes in the fetal liver in response to maternal folate depletion during pregnancy.

Similar Datasets

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