Maternal serum PFOA concentration and DNA methylation in cord blood: A pilot study.
Ontology highlight
ABSTRACT:
SUBMITTER: Kingsley SL
PROVIDER: S-EPMC5554452 | biostudies-literature | 2017 Oct
REPOSITORIES: biostudies-literature
Publications
Maternal serum PFOA concentration and DNA methylation in cord blood: A pilot study.
Kingsley Samantha L SL Kelsey Karl T KT Butler Rondi R Chen Aimin A Eliot Melissa N MN Romano Megan E ME Houseman Andres A Koestler Devin C DC Lanphear Bruce P BP Yolton Kimberly K Braun Joseph M JM
Environmental research 20170620
Perfluorooctanoic acid (PFOA), a perfluoroalkyl substance, is commonly detected in the serum of pregnant women and may impact fetal development via epigenetic re-programming. In a pilot study, we explored associations between serum PFOA concentrations during pregnancy and offspring peripheral leukocyte DNA methylation at delivery in women with high (n = 22, range: 12-26ng/mL) and low (n = 22, range: 1.1-3.1ng/mL) PFOA concentrations. After adjusting for cell type, child sex, and income, we did n ...[more]
Similar Datasets
Project description:Eating disorders (ED) are chronic psychiatric disorders, common amongst women of reproductive age. ED in pregnancy are associated with poor nutrition and abnormal intrauterine growth. Increasing evidence also shows offspring of women with ED have adverse developmental and birth outcomes. We sought to carry out the first study investigating DNA methylation in offspring of women with ED. We compared cord blood DNA methylation in offspring of women with active ED (n = 21), past ED (n = 43) and age- and social class-matched controls (n = 126) as part of the Avon Longitudinal Study of Parents and Children.Offspring of women with both active and past ED had lower whole-genome methylation compared to controls (active ED 49.1% (95% confidence intervals 50.5-47.7%), past ED 49.2% (95% CI 50.7-47.7.0%), controls 52.4% (95% CI 53.0%-51.0%)). Amongst offspring of ED women, those born to women with restrictive-type and purging-type ED had lower methylation levels compared to those of controls. Offspring of women with an active restrictive ED in pregnancy had lower whole-genome methylation compared to offspring of women with past restrictive ED. We observed decreased methylation at the DHCR24 locus in offspring of women with active pregnancy ED (effect size (ES) = -?0.124, p = 6.94 × 10-8) and increased methylation at the LGALS2 locus in offspring of women with past ED (ES = 0.07, p = 3.74 × 10-7) compared to controls.Maternal active and past ED are associated with differences in offspring whole-genome methylation. Our results show altered DNA methylation in loci relevant to metabolism; these might be biomarkers of disrupted metabolic pathways in offspring of ED mothers. Further work is needed to examine potential mechanisms and functional outcomes of the observed methylation patterns.
| S-EPMC5659017 | biostudies-other
Project description:The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N?=?100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P?=?0.032), EPDS score (P?=?0.007) and cortisol AUCgs at T2 (CAR: P?=?0.020; DAY: P?=?0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment.
| S-EPMC5015800 | biostudies-other
Project description:BACKGROUND:Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in cord blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in cord blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. RESULTS:Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36?weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (< 18?weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p < 0.05) when both CRP and methylation were measured at the same time point in cord blood. The top 7 CpGs most strongly associated with CRP resided in inflammation and vascular-related genes. CONCLUSIONS:Maternal CRP levels measured during each trimester were not associated with cord blood DNA methylation. Rather, DNA methylation was associated with CRP levels measured in cord blood, particularly in gene regions predominately associated with angiogenic and inflammatory pathways. TRIAL REGISTRATION:Clinicaltrials.gov, NCT00467363, Registered April 30, 2007, http://www.clinicaltrials.gov/ct2/show/NCT00467363.
| S-EPMC7193358 | biostudies-literature
Project description:Essential and non-essential elements deficiencies may lead to various birth complications. The aim of this paper was to determine calcium (Ca), copper (Cu), iron (Fe), potassium (K), magnesium (Mg), sodium (Na), phosphorus (P), lead (Pb), strontium (Sr), and zinc (Zn) concentrations in maternal blood and cord blood. Whole blood and cord blood samples collected from pregnant women (n = 136) were analyzed for the concentration of the elements by spectrophotometric atomic absorption in inductively coupled argon plasma (ICP-OES). The results showed that Ca, Pb, and Sr concentrations were similar in maternal and cord blood, while Fe and K levels were higher in cord blood than in maternal blood. The cord blood Cu, Na, and Zn concentrations were lower than those in maternal blood, suggesting transplacental transfer of these elements were limited. Moreover, checking the influence of studied elements on the anthropometric parameters of the newborns, we found that the highest number of associations was between Cu in cord blood. Due to the fact that the pregnant women were healthy, and the newborns were without any disorders, we suggest that the values obtained in our study are normal values of studied elements in whole blood and cord blood in patients from Poland.
| S-EPMC8656657 | biostudies-literature
Project description:Maternal nutrition is critically involved in the development and health of the fetus. We evaluated maternal methyl-group donor intake through diet (methionine, betaine, choline, folate) and supplementation (folic acid) before and during pregnancy in relation to global DNA methylation and hydroxymethylation and gene specific (IGF2 DMR, DNMT1, LEP, RXRA) cord blood methylation. A total of 115 mother-infant pairs were enrolled in the MAternal Nutrition and Offspring's Epigenome (MANOE) study. The intake of methyl-group donors was assessed using a food-frequency questionnaire. LC-MS/MS and pyrosequencing were used to measure global and gene specific methylation, respectively. Dietary intake of methyl-groups before and during pregnancy was associated with changes in LEP, DNMT1, and RXRA cord blood methylation. Statistically significant higher cord blood LEP methylation was observed when mothers started folic acid supplementation more than 6 months before conception compared with 3-6 months before conception (34.6 ± 6.3% vs. 30.1 ± 3.6%, P = 0.011, LEP CpG1) or no folic acid used before conception (16.2 ± 4.4% vs. 13.9 ± 3%, P = 0.036 for LEP CpG3 and 24.5 ± 3.5% vs. 22.2 ± 3.5%, P = 0.045 for LEP mean CpG). Taking folic acid supplements during the entire pregnancy resulted in statistically significantly higher cord blood RXRA methylation as compared with stopping supplementation in the second trimester (12.3 ± 1.9% vs. 11.1 ± 2%, P = 0.008 for RXRA mean CpG). To conclude, long-term folic acid use before and during pregnancy was associated with higher LEP and RXRA cord blood methylation, respectively. To date, pregnant women are advised to take a folic acid supplement of 400 µg/day from 4 weeks before until 12 weeks of pregnancy. Our results suggest significant epigenetic modifications when taking a folic acid supplement beyond the current advice.
| S-EPMC5270634 | biostudies-literature
Project description:BackgroundArsenic is an epigenetic toxicant and could influence fetal developmental programming.ObjectivesWe evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.MethodsDrinking-water and urine samples were collected when women were at ? 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure.ResultsMean (± SD) drinking-water arsenic concentration was 14.8 ± 36.2 ?g/L (range: < 1-230 ?g/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation.ConclusionsExposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effects.
| S-EPMC3404653 | biostudies-literature
Project description:Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples. Cord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in eight individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition. DNA methylation PCs were associated with individual (PPC1 = 1.4 × 10-9; PPC2 = 2.9 × 10-5; PPC3 = 3.8 × 10-5; PPC4 = 4.2 × 10-6; PPC5 = 9.9 × 10-13, PPC6 = 1.3 × 10-11) and not with sample type (PPC1-6>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired samples ranged from r = 0.66 to r = 0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (five sites had unadjusted P<10-5). Estimated cell type proportions did not differ by sample type (P = 0.46), and estimated proportions were highly correlated between paired samples (r = 0.99). Differences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.
| S-EPMC5836975 | biostudies-literature
Project description:Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array.Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods.Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing.
| S-EPMC5526324 | biostudies-literature
Project description:Maternal prenatal exposures, including bisphenol A (BPA), are associated with offspring's risk of disease later in life. Alterations in DNA methylation may be a mechanism through which altered prenatal conditions (e.g. maternal exposure to environmental toxicants) elicit this disease risk. In the Michigan Mother and Infant Pairs Cohort, maternal first-trimester urinary BPA, bisphenol F, and bisphenol S concentrations were tested for association with DNA methylation patterns in infant umbilical cord blood leukocytes (N = 69). We used the Illumina Infinium MethylationEPIC BeadChip to quantitatively evaluate DNA methylation across the epigenome; 822 020 probes passed pre-processing and quality checks. Single-site DNA methylation and bisphenol models were adjusted for infant sex, estimated cell-type proportions (determined using cell-type estimation algorithm), and batch as covariates. Thirty-eight CpG sites [false discovery rate (FDR) <0.05] were significantly associated with maternal BPA exposure. Increasing BPA concentrations were associated with lower DNA methylation at 87% of significant sites. BPA exposure associated DNA methylation sites were enriched for 38 pathways significant at FDR <0.05. The pathway or gene-set with the greatest odds of enrichment for differential methylation (FDR <0.05) was type I interferon receptor binding. This study provides a novel understanding of fetal response to maternal bisphenol exposure through epigenetic change.
| S-EPMC7757124 | biostudies-literature
Project description:In utero environmental perturbations have been associated with epigenetic changes in the offspring and a lifelong susceptibility to cardiovascular diseases (CVD). DNA methylation at the ATP-binding cassette transporter A1 (ABCA1) gene was previously associated with CVD, but whether these epigenetic marks respond to changes in the maternal environment is unknown. This study was undertaken to assess the associations between the maternal metabolic profile and ABCA1 DNA methylation levels in placenta and cord blood. Placenta and cord blood samples were obtained at delivery from 100 women including 26 with impaired glucose tolerance (IGT) diagnosed following a 75 g-oral glucose tolerance test (OGTT) between week 24 and 28 of gestation. ABCA1 DNA methylation and mRNA levels were measured using bisulfite pyrosequencing and quantitative real-time PCR, respectively. We report that ABCA1 DNA methylation levels on the maternal side of the placenta are correlated with maternal high density lipoprotein cholesterol (HDL-C) levels (r<-0.21; P<0.04) and glucose levels 2 h post-OGTT (r = 0.25; P = 0.02). On the fetal side of the placenta, ABCA1 DNA methylation levels are associated with cord blood triglyceride levels (r = -0.28; P = 0.01). ABCA1 DNA methylation variability on both sides of the placenta are also associated with ABCA1 mRNA levels (r<-0.35; P = 0.05). As opposed to placenta, cord blood DNA methylation levels are negatively correlated with maternal glucose 2 h post-OGTT (r = -0.26; P = 0.02). In conclusion, the epivariations observed in placenta and cord blood likely contribute to an optimal materno-fetal cholesterol transfer. These in utero epigenetics adaptations may also potentially trigger the long-term susceptibility of the newborn to dyslipidemia and CVD.
| S-EPMC3933490 | biostudies-literature