Prenatal Exposure to Cadmium and Cotinine and CpG island DNA methylation in Mother-Infant Pairs.
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ABSTRACT:
SUBMITTER: Gona S
PROVIDER: S-EPMC4538703 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Cadmium (Cd) is prevalent in the environment yet understudied as a developmental toxicant. Cd partially crosses the placental barrier from mother to fetus and is linked to detrimental effects in newborns. Here we examine the relationship between levels of Cd during pregnancy and 5-methylcytosine (5mC) levels in leukocyte DNA collected from 17 mother-newborn pairs. The methylation of cytosines is an epigenetic mechanism known to impact transcriptional signaling and influence health endpoints. A methylated cytosine-guanine (CpG) island recovery assay was used to assess over 4.6 million sites spanning 16,421 CpG islands. Exposure to Cd was classified for each mother-newborn pair according to maternal blood levels and compared with levels of cotinine. Subsets of genes were identified that showed altered DNA methylation levels in their promoter regions in fetal DNA associated with levels of Cd (n = 61), cotinine (n = 366), or both (n = 30). Likewise, in maternal DNA, differentially methylated genes were identified that were associated with Cd (n = 92) or cotinine (n = 134) levels. While the gene sets were largely distinct between maternal and fetal DNA, functional similarities at the biological pathway level were identified including an enrichment of genes that encode for proteins that control transcriptional regulation and apoptosis. Furthermore, conserved DNA motifs with sequence similarity to specific transcription factor binding sites were identified within the CpG islands of the gene sets. This study provides evidence for distinct patterns of DNA methylation or "footprints" in fetal and maternal DNA associated with exposure to Cd.
| S-EPMC3962531 | biostudies-other
Project description:The main source of mercury (Hg) exposure in the general population is fish. Another possible source is dental amalgam. Here, we compare the levels of Hg and selenium (Se) in samples of maternal and fetal origin collected shortly after childbirth of healthy postpartum women in the coastal (n = 96) and continental (n = 185) areas of Croatia related to maternal seafood/fish consumption. We also evaluated Hg concentrations and maternal serum metallothionein (MT2) concentrations in relation to the number of dental amalgam fillings, and MT2A-5A/G (rs28366003) polymorphism. The levels of Hg and Se in maternal hair and blood/serum, placenta and cord blood/serum increased in relation to increasing fish consumption with the highest values in subjects from the coast. The concentrations of each element and between elements correlated across the matrices. Increasing amalgam number correlated linearly with increased Hg levels in maternal and cord serum and was not associated with serum MT2. No association of MT2A-5A/G polymorphism and Hg or Se levels were found. The results confirmed higher fish consumption in coastal vs. continental Croatia and increases of both Hg and Se related to fish consumption in all analyzed samples. Increased blood Hg reflected the predominant MeHg share from seafood, while increased serum Hg matched exposure from dental amalgams.
| S-EPMC7355586 | biostudies-literature
Project description:BackgroundSmoking while pregnant is associated with a myriad of negative health outcomes in the child. Some of the detrimental effects may be due to epigenetic modifications, although few studies have investigated this hypothesis in detail.ObjectivesTo characterize site-specific epigenetic modifications conferred by prenatal smoking exposure within asthmatic children.MethodsUsing Illumina HumanMethylation27 microarrays, we estimated the degree of methylation at 27,578 distinct DNA sequences located primarily in gene promoters using whole blood DNA samples from the Childhood Asthma Management Program (CAMP) subset of Asthma BRIDGE childhood asthmatics (n?=?527) ages 5-12 with prenatal smoking exposure data available. Using beta-regression, we screened loci for differential methylation related to prenatal smoke exposure, adjusting for gender, age and clinical site, and accounting for multiple comparisons by FDR.ResultsOf 27,578 loci evaluated, 22,131 (80%) passed quality control assessment and were analyzed. Sixty-five children (12%) had a history of prenatal smoke exposure. At an FDR of 0.05, we identified 19 CpG loci significantly associated with prenatal smoke, of which two replicated in two independent populations. Exposure was associated with a 2% increase in mean CpG methylation in FRMD4A (p?=?0.01) and Cllorf52 (p?=?0.001) compared to no exposure. Four additional genes, XPNPEP1, PPEF2, SMPD3 and CRYGN, were nominally associated in at least one replication group.ConclusionsThese data suggest that prenatal exposure to tobacco smoke is associated with reproducible epigenetic changes that persist well into childhood. However, the biological significance of these altered loci remains unknown.
| S-EPMC4070909 | biostudies-literature
Project description:Epigenetic silencing associated with aberrant methylation of promoter region CpG islands is one mechanism leading to loss of tumor suppressor function in human cancer. Profiling of CpG island methylation indicates that some genes are more frequently methylated than others, and that each tumor type is associated with a unique set of methylated genes. However, little is known about why certain genes succumb to this aberrant event. To address this question, we used Restriction Landmark Genome Scanning to analyze the susceptibility of 1,749 unselected CpG islands to de novo methylation driven by overexpression of DNA cytosine-5-methyltransferase 1 (DNMT1). We found that although the overall incidence of CpG island methylation was increased in cells overexpressing DNMT1, not all loci were equally affected. The majority of CpG islands (69.9%) were resistant to de novo methylation, regardless of DNMT1 overexpression. In contrast, we identified a subset of methylation-prone CpG islands (3.8%) that were consistently hypermethylated in multiple DNMT1 overexpressing clones. Methylation-prone and methylation-resistant CpG islands were not significantly different with respect to size, C+G content, CpG frequency, chromosomal location, or promoter association. We used DNA pattern recognition and supervised learning techniques to derive a classification function based on the frequency of seven novel sequence patterns that was capable of discriminating methylation-prone from methylation-resistant CpG islands with 82% accuracy. The data indicate that CpG islands differ in their intrinsic susceptibility to de novo methylation, and suggest that the propensity for a CpG island to become aberrantly methylated can be predicted based on its sequence context.
| S-EPMC218745 | biostudies-literature
Project description:Paracetamol exposure has been positively associated with asthma development. The relative importance of prenatal vs infant exposure and confounding by indication remains elusive. We examined the association of prenatal and infant (first 6 months) paracetamol exposure with asthma development while addressing confounding by indication.We used information from the Norwegian Mother and Child Cohort Study, including 53169 children for evaluation of current asthma at 3 years, 25394 for current asthma at 7 years and 45607 for dispensed asthma medications at 7 years in the Norwegian Prescription Database. We calculated adjusted relative risks (adj. RR) and 95% confidence intervals (CI) using log-binomial regression.There were independent modest associations between asthma at 3 years with prenatal paracetamol exposure (adj. RR 1.13; 95% CI: 1.02-1.25) and use of paracetamol during infancy (adj. RR 1.29; 95% CI: 1.16-1.45). The results were consistent for asthma at 7 years. The associations with prenatal paracetamol exposure were seen for different indications (pain, respiratory tract infections/influenza and fever). Maternal pain during pregnancy was the only indication that showed an association both with and without paracetamol use. Maternal paracetamol use outside pregnancy and paternal paracetamol use were not associated with asthma development. In a secondary analysis, prenatal ibuprofen exposure was positively associated with asthma at 3 years but not asthma at 7 years.This study provides evidence that prenatal and infant paracetamol exposure have independent associations with asthma development. Our findings suggest that the associations could not be fully explained by confounding by indication.
| S-EPMC5841883 | biostudies-other
Project description:The biological mechanism of cadmium's effects is poorly characterized. This data was generated in order to help better understand the epigenetic role that Cadmium plays. We used the MIRA assay and the Affymetrix Human Promoter 1.0R Array in order to measure methylation levels in promoter regions.
2015-04-17 | GSE67976 | GEO
Project description:We compare the methylation status of CpG island clones by MeDIP in SW48 colon cancer cells relative to normal colon mucosa and WI38 primary fibroblasts. Keywords: ordered
2005-07-03 | GSE2653 | GEO
Project description:The biological mechanism of cadmium's effects is poorly characterized. This data was generated in order to help better understand the epigenetic role that Cadmium plays. We used the MIRA assay and the Affymetrix Human Promoter 1.0R Array in order to measure methylation levels in promoter regions. 34 samples corresponding to 17 mother-infant pairs were selected based upon measured levels of cadmium in the blood. Methylated DNA fragments were then isolated, amplified, and run on the Affymetrix Human Promoter 1.0R Array. Results were then summarized to CpG islands for each sample.
2015-04-17 | E-GEOD-67976 | biostudies-arrayexpress
Project description:We compare the methylation status of CpG island clones by MeDIP in SW48 colon cancer cells relative to normal colon mucosa and WI38 primary fibroblasts.
2010-06-09 | E-GEOD-2653 | biostudies-arrayexpress
Project description:Persistent organic pollutants (POPs) are believed to alter metabolic homeostasis during fetal development, leading to childhood obesity. However, limited studies have explored how fetal chemical exposures relate to birth and infant weight outcomes in low-income Hispanic families at the highest risk of obesity. Therefore, we sought to determine associations between neonatal POPs exposure measured in newborn dried blood spots (DBS) and prenatal diet quality, birth weight, and overweight status at 18 months old. We conducted a case-control study nested within the Starting Early Program randomized controlled trial comparing POPs concentrations in infants with healthy weight (n = 46) and overweight status (n = 52) at age 18 months. Three categories of POPs, organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) were measured in archived newborn DBS. We assessed correlations between prenatal diet quality and neonatal POPs concentrations. Multivariable regression analyses examined associations between POPs (dichotomized at the mean) and birth weight z-score and weight status at 18 months, controlling for confounders. Seven of eight chemicals had detectable levels in greater than 94% of the sample. Higher protein, sodium and refined grain intake during pregnancy were correlated with lower POPs in newborn DBS. We found that high concentrations of perfluorooctanesulfonate (unstandardized coefficient [B]: -0.62, 95% confidence interval [CI]: -0.96 to -0.29) and perfluorohexanesulfate (B: -0.65, 95% CI: -0.99 to -0.31) were related to lower birth weight z-scores compared to those with low concentrations. We did not find associations between PBDEs, OCPs, and the other PFASs with birth weight z-scores, or between any POPs and weight status at 18 months. In conclusion, two PFASs were associated with lower birth weight, an important indicator of child health and growth, although direct associations with infant overweight status were not found. Whether neonatal POPs exposures contribute to economic and ethnic disparities in early obesity remains unclear.
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