Transcriptomics in response to internal exposure in Flemisch adults
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE44422 | GEO | 2013/02/21
SECONDARY ACCESSION(S): PRJNA189943
REPOSITORIES: GEO
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Project description:Genome wide DNA methylation profiling of cord blood in Faroe Island cohort. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,000 CpGs in cord blood samples. Background: Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from chemical exposures. Objective: We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. Method: We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood. The cord blood DNA methylome was profiled using Infinium Methylation 450K BeadChips. We determined the associations of CpG site changes with concentrations of MeHg, major PCBs, other organochlorine compounds, (hexachlorobenzene [HCB], p,p’-dichlorodiphenyldichloroethylene [p,p’-DDE] and p,p’-dichlorodiphenyltrichloroethane) and perfluoroalkyl substances. Results: In a combined sex analysis, among the 16 chemicals studied, PCB congener 105 (CB-105) exposure was associated with the majority of differentially methylated CpG sites (214 out of a total of 250). In female-only-analysis, only 73 CB-105 associated CpG sites were detected, 44 of which were mapped to genes in the ELAV1-associated cancer network. In males-only, methylation changes were seen for perfluorooctane sulfonate, HCB, and p,p’-DDE in 10,598; 1,238; and 1,473 CpG sites, respectively, 15% of which were enriched in cytobands of the X chromosome associated with neurological disorders. Conclusion: In this multiple-pollutant and genome-wide study, we identified key epigenetic toxicants. The significant enrichment of specific X-chromosome sites in males implies potentially sex-specific epigenome responses to prenatal chemical exposures.
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Project description:Thicklip grey mullet hepatic transcriptome comparission from PASAIA harbour, Basque Country Active biomonitoring using sentinel species caged in differentially polluted aquatic environments is being implemented worldwide. To determine the biological effects of pollutants in a heavily polluted Basque harbour (Pasaia, 431700N 015500W), two cages specially designed to deploy thicklip grey mullets (Chelon labrosus) were placed in the inner- and outer-harbour. Cages were deployed for 5 and 21 days to determine possible differences between sites, linked to specific chemical burdens. Hepatic gene expression profiles were studied using Q-PCR and a toxicology tailored low density mullet microarray (160 genes). Chemical analysis showed high concentrations of metals, PAHs, PCBs, phthalates, and organometallic compounds at both sites, most chemicals showing slightly higher concentrations in the inner-harbour. Q-PCR expression studies confirmed chemical data as metallothionein and CYP1A showed significant expression upregulation at day 21 at both sites, but showed no differences between sites. The microarray showed gene expression profiles that were able to distinguish mullets according to the site they were deployed in and the day they were captured. Regarding sites, 39 genes showed significant differences at p<0.05 on the last sampling day. Two families of genes are to be highlighted. Phase I and II biotransformation genes CYP2, CYP3 and UGT were upregulated in the inner-harbour together with AhR2 and AhRR. Similarly, TBT binding protein and genes involved in lipid metabolism such us PPARa and CYP7 were upregulated. The latter two genes have also been reported to be regulated by TBT. In summary, the low density microarray designed for mullets proved to be useful to unveil even slight differences in pollutant burdens in field conditions. 24 samples:6 hepatic samples from Inner harbour after 3 days of exposure, 6 hepatic samples from outer harbour after 3 days of exposure, 6 hepatic samples from Inner harbour after 15 days of exposure and 6 hepatic samples from outer harbour after 15 days of exposure
2016-07-31 | E-GEOD-36281 | biostudies-arrayexpress
Project description:Thicklip grey mullet hepatic transcriptome comparission from PASAIA harbour, Basque Country Active biomonitoring using sentinel species caged in differentially polluted aquatic environments is being implemented worldwide. To determine the biological effects of pollutants in a heavily polluted Basque harbour (Pasaia, 431700N 015500W), two cages specially designed to deploy thicklip grey mullets (Chelon labrosus) were placed in the inner- and outer-harbour. Cages were deployed for 5 and 21 days to determine possible differences between sites, linked to specific chemical burdens. Hepatic gene expression profiles were studied using Q-PCR and a toxicology tailored low density mullet microarray (160 genes). Chemical analysis showed high concentrations of metals, PAHs, PCBs, phthalates, and organometallic compounds at both sites, most chemicals showing slightly higher concentrations in the inner-harbour. Q-PCR expression studies confirmed chemical data as metallothionein and CYP1A showed significant expression upregulation at day 21 at both sites, but showed no differences between sites. The microarray showed gene expression profiles that were able to distinguish mullets according to the site they were deployed in and the day they were captured. Regarding sites, 39 genes showed significant differences at p<0.05 on the last sampling day. Two families of genes are to be highlighted. Phase I and II biotransformation genes CYP2, CYP3 and UGT were upregulated in the inner-harbour together with AhR2 and AhRR. Similarly, TBT binding protein and genes involved in lipid metabolism such us PPARa and CYP7 were upregulated. The latter two genes have also been reported to be regulated by TBT. In summary, the low density microarray designed for mullets proved to be useful to unveil even slight differences in pollutant burdens in field conditions.
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