TCDD-mediated multigenerational effects in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA909233 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:TCDD exposure cauuses multigenerational effect in mice.
2023-01-18 | GSE220204 | GEO
Project description:Exposure to TCDD early in development produces reproductive abnormalities and decreased reproductive capacity in males in subsequent generations We used microarrays to investigate the global programme of gene expression in testicular tissue and identified distinct multigenerational and transgenerational gene expression changes due to legacy TCDD exposure in males.
2018-10-01 | GSE111446 | GEO
Project description:Exposure to TCDD early in development produces reproductive abnormalities and decreased reproductive capacity in males in subsequent generations. We used WGBS to investigate differential methylation in testicular tissue and identified distinct multigenerational and transgenerational methylation changes due to legacy TCDD exposure in males.
2022-04-20 | GSE149919 | GEO
Project description:2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant. Previous reports revealed TCDD activating aryl hydrocarbon receptor (AhR) pathway and causing cardiac damage. However, the mechanism of AhR-induced cardiac defect in response to TCDD exposure remains unclear. In this study, we characterized the impacts of TCDD exposure on heart morphology and cardiac function in zebrafish. To investigate the differentially expressed genes under TCDD exposure, we collected the zebrafish larave heart from the control and TCDD treatment groups. We then performed gene expression profiling analysis using data obtained from RNA-seq. Transcriptomic profiling showed that, along with an upregulation of the AhR signaling pathway by TCDD, the expression of pro-ferroptosis genes was upregulated, while genes implicated in glutathione metabolism were downregulated. Consistently, lipid peroxidation, as indicated by malonaldehyde (MDA) production, increased in TCDD-exposed cardiac tissue. Accordingly, inhibiting lipid peroxidation with Liproxstatin-1 reversed the adverse cardiac effects under TCDD treatment. Together, our findings demonstrate that AhR-mediated lipid peroxidation contributes to the cardiac developmental defects of TCDD during zebrafish early development.
2022-10-30 | GSE206948 | GEO
Project description:2,3,7,8–tetrachlorodibenzo-p-dixion (TCDD) is the most potent of the dioxin congeners, capable of causing a wide range of toxic effects across numerous animal models. Previous studies have demonstrated that males and females of the same species can display divergent sensitivity phenotypes to TCDD toxicities. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the aryl hydrocarbon receptor (AHR), the mechanism of differential responses to TCDD exposure between sexes remains largely unknown. To investigate the differential sensitivities in male and female mice, we profiled the hepatic transcriptomic responses 4 days following exposure to various amounts of TCDD (125, 250, 500 or 1000 µg/kg) in adult male and female C57BL/6Kuo mice. Several key findings were revealed by our study. 1) Hepatic transcriptomes varied significantly between the sexes at all doses examined. 2) The liver transcriptome of males was more dysregulated by TCDD than that of females. 3) The alteration of ‘AHR-core’ genes was consistent in magnitude, regardless of sex. 4) A subset of genes demonstrated sex-dependent TCDD-induced transcriptional changes, including Fmo3 and Nr1i3, which were significantly induced in livers of male mice only. In addition, a meta-analysis was performed to contrast transcriptomic profiles of various organisms and tissues following exposure to equitoxic doses of TCDD. Minimal overlap was observed in the differences between TCDD-sensitive or TCDD-resistant models. Sex-dependent sensitivities to TCDD exposure are associated with a set of sex-specific TCDD-responsive genes. In addition, complex interactions between the aryl hydrocarbon and sex hormone receptors may affect the observable differences in sensitivity phenotypes between the sexes. Further work is necessary to better understand the roles of those genes altered by TCDD in a sex-dependent manner, and their association with changes to sex hormones and receptors.
2015-03-01 | GSE61038 | GEO
Project description:2,3,7,8M-bM-^@M-^Stetrachlorodibenzo-p-dixion (TCDD) is a dioxin congener that causes a wide range of toxic effects in rodent species. Previous studies discovered that males and females of the same species display different sensitivities to TCDD exposure. Although it is now clear that most TCDD-induced toxic outcomes are mediated by the Aryl Hydrocarbon Receptor (AHR), a transcription factor, the mechanism of sex-specific responses to TCDD remains largely unknown. To understand the differential sensitivity in male and female animals, we profiled the hepatic transcriptomic responses to single doses of TCDD (125, 250, 500, or 1000 M-BM-5g/kg) in male and female C57BL6 mice. Several key findings were revealed by our study: 1) transcriptomic profiles varied largely between sexes at all doses; 2) the mRNA abundance profiles of female mice were less altered from basal level; 3) the alteration of M-bM-^@M-^XAHR-coreM-bM-^@M-^Y genes were consistent regardless of sex; 4) a list of sex-specific TCDD-responsive genes were identified, including Fmo3 and Nr1i3 upregulated in male mice and Sult3a1 downregulated in female mice; 5) functional analysis of these candidate genes showed various biological pathway enrichments in a sex-dependent manner. Our study shows that the sex-dependent sensitivities to TCDD exposure are associated with a set of sex-specific TCDD-responsive genes that are indirectly regulated by AHR activity. The exact roles of these genes in response to TCDD exposure are not clear and require further investigation. Adult male and female C57BL/6 mice were treated by gavage with one single-dose TCDD (125, 250, 500, or 1000 M-NM-<g/kg) in corn oil or corn oil vehicle alone. Animals were euthanized at 96 hours after treatment and tissues were harvested. RNA was isolated from hepatic tissue and the transcriptome for each animal assayed on an individual microarray.
2015-03-01 | E-GEOD-61038 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) mediates most of the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, TCDD toxicity phenotypes vary widely between species, strains and even between sexes within a strain. While the exact reasons for this variation remain unclear, it is thought to be related to differences in the structure of the AHR. Previous studies comparing the downstream effects of TCDD exposure between animals with different AHR isoforms have been confounded by the genetic differences between these model systems. To address this issue conclusively, we evaluated three transgenic mouse lines, each of which express a different rat AHR isoform (rWT, DEL, and INS) from two strains of rat with highly divergent TCDD-susceptibilities, within identical genetic backgrounds. Here we profile hepatic transcriptomic responses following exposure to TCDD, and use these to identify transcripts associated with toxicity. We have confirmed that the variation in toxicity is inherent to the AHR isoform. Additionally, we note the enhanced activity of the modified transactivation domain of the DEL isoform, relative to the INS isoform, and provide further evidence that the INS isoform is responsible for the high resistance to TCDD observed in H/W rats. We also uncover several candidate genes that were consistently differentially expressed in TCDD-sensitive mice and rats. Adult male transgenic mice were treated by gavage with 0, 125, 250, 500, or 1000 µg/kg TCDD dissolved in corn oil vehicle. Mice were euthanized 4 days following treatment and liver tissue was harvested for analysis. RNA was isolated and the transcriptome for each animal assayed on separate microarrays.
2016-07-03 | E-GEOD-72270 | biostudies-arrayexpress
Project description:The aryl hydrocarbon receptor (AHR) mediates most of the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, TCDD toxicity phenotypes vary widely between species, strains and even between sexes within a strain. While the exact reasons for this variation remain unclear, it is thought to be related to differences in the structure of the AHR. Previous studies comparing the downstream effects of TCDD exposure between animals with different AHR isoforms have been confounded by the genetic differences between these model systems. To address this issue conclusively, we evaluated three transgenic mouse lines, each of which express a different rat AHR isoform (rWT, DEL, and INS) from two strains of rat with highly divergent TCDD-susceptibilities, within identical genetic backgrounds. Here we profile hepatic transcriptomic responses following exposure to TCDD, and use these to identify transcripts associated with toxicity. We have confirmed that the variation in toxicity is inherent to the AHR isoform. Additionally, we note the enhanced activity of the modified transactivation domain of the DEL isoform, relative to the INS isoform, and provide further evidence that the INS isoform is responsible for the high resistance to TCDD observed in H/W rats. We also uncover several candidate genes that were consistently differentially expressed in TCDD-sensitive mice and rats.
2016-01-01 | GSE72270 | GEO
Project description:Confluent C3H10T1/2 cells stimulated to differentiate using IDMB (1uM BRL49653, 1uM Dexamethasone, 0.5uM IBMX, 10ug/mL Insulin). Expression was examined 24 hours after IDMB treatment. Additionally, the effects of addition of TCDD 48 hours prior to IDMB treatment, and EGF addition concurrent with IDMB treatment were examined. Keywords = Adipogenesis Keywords = TCDD Keywords = EGF Keywords: repeat sample
2004-03-25 | GSE1123 | GEO
Project description:Targeted proteomics using an inclusion list in a data-dependent acquisition method. Mouse prostates were analyzed to determine the effects of developmental exposure to the dioxin TCDD after hormone treatment
2020-03-30 | PXD014752 | Pride