Serum Dioxin and DNA Methylation in the Sperm of Operation Ranch Hand Veterans Exposed to Agent Orange
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE139307 | GEO | 2019/10/24
REPOSITORIES: GEO
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Project description: Not available
| S-EPMC6819394 | biostudies-literature
Project description:Serum Dioxin and DNA Methylation in the Sperm of Operation Ranch Hand Veterans Exposed to Agent Orange
| PRJNA579174 | ENA
Project description:Dioxin is one of the most common historic industrial contaminants with several major industry and government accidents having exposed large numbers of the worldwide population over the past century. Previous rat studies have demonstrated the ability of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) exposure to promote the epigenetic transgenerational inheritance of disease susceptibility in subsequent generations. The types of disease observed include testis, ovary, kidney, prostate and obesity pathologies. The current study was designed to use an epigenome-wide association study (EWAS) to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. The transgenerational F3 generation dioxin lineage male rats with and without a specific disease were compared to identify differential DNA methylation regions (DMRs). The genomic features of the DMRs are characterized. Observations demonstrate that disease specific epimutation DMRs exist for the transgenerational dioxin lineage rats that can potentially be used as epigenetic biomarkers for testis, ovary, kidney, prostate and obesity diseases. These disease specific DMRs were associated with genes that have previously been shown to be linked with these diseases. This EWAS for transgenerational disease identified epigenetic biomarkers and provides the proof of concept of the potential to develop similar biomarkers for humans to diagnose disease susceptibilities and facilitate preventative medicine.
2020-12-02 | GSE157539 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE15857: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Kidney GSE15858: The Aryl Hydrocarbon Receptor Regulates Tissue-Specific Dioxin-Dependent and Dioxin-Independent Gene Batteries: Liver Refer to individual Series
2010-05-05 | E-GEOD-15859 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology. Two-Factor, Two-Level. AHRnull and wildtype mice were treated with dioxin (TCDD) or corn oil vehicle. 3 replicates per treatment for AHRnull mice, 6 replicates of dioxin treatment for wildtype mice, and 5 replicates of corn oil treatment for wildtype mice.
2009-09-21 | E-GEOD-15858 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology.
2009-09-21 | GSE15858 | GEO
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology.
2009-09-21 | GSE15857 | GEO
Project description:The aryl hydrocarbon receptor (AHR) is a widely-expressed ligand-dependent transcription-factor that mediates cellular responses to dioxins and other planar aromatic hydrocarbons. Indeed, AHR-null mice are refractory to the physiological effects of dioxin-exposure. Although some mechanistic aspects of AHR activity are well understood, the tissue-specificity of AHR effects remains unclear, both during development and following administration of exogenous ligands. Previously we employed studied the transcriptional responses of wild-type and AHR-null C57BL/6J mice to dioxin-exposure. We found that essentially all hepatic effects of dioxin were mediated by the AHR, and that large numbers of genes were affected by dioxin exposure. Surprisingly, we also identified a large effect of AHR genotype, even in the absence of dioxin-exposure. To help assess the tissue-specificity of AHR activity we replicated that prior study in the kidney from the same animals previously studied, and extensively compared the hepatic and renal transcriptional profiles. We find that dioxin-exposure causes essentially no transcriptional effects in the absence of a functional AHR in either liver or kidney. Surprisingly, aside from a number of well-established AHR target genes, dioxin-exposure has few effects in animals harbouring a wild-type AHR. By contrast, AHR genotype profoundly remodels the renal transcriptome, and is associated with perturbation of specific functional pathways and with specific DNA motifs. Our results demonstrate the importance of inter-tissue comparisons and highlight the basal role of AHR activity in renal and hepatic development or normal physiology. Two-Factor, Two-Level. AHRnull and wildtype mice were treated with dioxin (TCDD) or corn oil vehicle. 3 replicates per treatment for AHRnull mice, and 6 replicates per treatment for wildtype mice.
2009-09-21 | E-GEOD-15857 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that mediates the toxic effects of the environmental contaminant, dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD). Dioxin causes a diverse range of toxic responses, including hepatic damage and lethal wasting syndrome; however, the mechanisms of dioxin-induced toxicity are still unknown. Here we show that the loss of TCDD-inducible poly(ADP-ribose) polymerase (TIPARP; ARTD14), an ADP-ribosyltransferase and AHR repressor, increases sensitivity to dioxin-induced toxicity and lethality. Tiparp-/- mice treated with a single injection of 100 mg/kg dioxin display an accelerated lethal wasting syndrome with no Tiparp-/- mice surviving beyond day 5; all Tiparp+/+ mice survived up to 30 days post treatment. Tiparp-/- mice displayed dramatic increases in liver steatosis and hepatotoxicity. At the molecular level, TIPARP selectively ADP-ribosylates AHR, but not AHR nuclear translocator (ARNT) and the Tiparp-dependent repression of AHR is reversed by the ADP-ribosylase and macrodomain containing protein MacroD1, but not MacroD2. These results describe previously unidentified roles for Tiparp, MacroD1, and ADP-ribosylation in AHR signaling, dioxin toxicity and lethality.
2015-05-14 | GSE61534 | GEO
Project description:We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of three dioxin-like compounds, two Polycyclic aromatic hydrocarbons (PAHs), Benzo(a)pyrene, Benzo(k) fluoranthene and b-naphthoflavone on the developing zebrafish embryo. The main goal is to distinguish the pattern of action of the chemical compounds and their needs varying the times of exposure. The results suggest a variety of MoA for different dioxin-like compounds, probably related to the nature and number of benzene rings. About 5% genes were affected by the treatment. Gene ontology (GO) analyses show that these genes are involved in the oxidation-reduction process. Representatives of each GO functional groups were selected and quantified by real-time PCR to validate the microarray data and to differentiate the action of dioxin-like compounds studied.
2015-12-31 | GSE41334 | GEO