Transcriptional responses to maternal trichloroethylene and/or N-acetyl cysteine exposure in Wistar rat placental tissue
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE168232 | GEO | 2022/06/01
REPOSITORIES: GEO
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Project description:Trichloroethylene (TCE) is a widely used industrial chemical, and a common environmental contaminant. It is a well-known carcinogen in rodents and a probable carcinogen in humans. Studies utilizing panels of mouse inbred strains afford a unique opportunity to understand both metabolic and genetic basis for differences in responses to TCE. We tested the hypothesis that individual and liver-specific toxic effects of TCE are genetically controlled and that the mechanisms of toxicity and susceptibility can be uncovered by exploring responses to TCE using a diverse panel of inbred mouse strains. TCE (2100 mg/kg) or corn oil vehicle were administered by gavage to 6-8 wk old male mice of 15 mouse strains. Serum and liver were collected at 2, 8, and 24 hr post dosing and were analyzed for TCE metabolites, hepatocellular injury and gene expression of liver. TCE metabolism, as evident from the levels of individual oxidative and conjugative metabolites, varied considerably between strains. TCE treatment-specific effect on the liver transcriptome was strongly dependent on the individual’s genetic background. PPAR-mediated molecular networks, consisting of the metabolism genes known to be induced by TCE, represent some of the most pronounced molecular effects of TCE treatment in mouse liver that are dependent on the individual’s genetic background. Conversely, cell death, liver necrosis, and immune mediated response pathways which are affected by TCE treatment in liver are largely genetic background-independent. These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance. 16 mouse strains were studied, vehicle control and mice treated by gavage with 2100 mg/kg Trichloroethylene and sacrificed 24 hrs after dosing
2011-02-01 | E-GEOD-24278 | biostudies-arrayexpress
Project description:To know if Trichloroethylene (TCE) can induce miRNA expression changes in mouse liver, we use microarray to screen for differentially expressed miRNAs in the liver of mice exposed to TCE at a dose of 1000 mg/kg b.w. for 5days . In our results, nine miRNAs were selected by volcano plot filtering (fold change ≥ 2 and P-value ≤ 0.05), out of which eight were up-regulated and one was down-regulated. The differential expression of miR-182-5p, miR-34a-5p and miR-451a were validated by qPCR.
2016-11-22 | GSE85904 | GEO
Project description:To examine changes, if any, in the expression of mRNAs in the liver tissue of mice, we have employed whole genome microarray expression profiling as a discovery platform to identify genes responsive to Trichloroethylene (TCE) treatment. In our results, the expression levels of 431 mRNAs were changed after TCE exposure, of which 291 were up-regulated and 140 were down-regulated. Using qPCR, we validated six of the mRNA expression changed genes, viz., Jun, Cdkn1a, Rad51b, Uhrf1, Svil and Ihh. Six B6C3F1 male mice were oral administrated with either corn oil or TCE (dissolved in corn oil, 1000mg/kg b.w per day) for 5 days. The expression changes of mRNAs in TCE exposured mouse liver were screened by whole genome microarray expression profiling and were validated by qPCR.
2014-11-14 | E-GEOD-58819 | biostudies-arrayexpress
Project description:Purpose: Trichloroethylene (TCE) and tetrachloroethylene (PCE) are ubiquitous environmental contaminants and occupational health hazards. The goals of this study were to establish the common and differing transcriptional effects of TCE and PCE. This study examined liver and kidney effects of TCE and PCE in a dose-response study design. Methods: Equi-molar doses of TCE (24, 80, 240, 800 mg/kg) or PE (30, 100, 300, 1,000 mg/kg) were administered by gavage in aqueous vehicle to male B6C3F1/J mice. Tissues were collected 24 hrs after exposure. Trichloroacetic acid (TCA), a major oxidative metabolite of both compounds, was measured and RNA sequencing was performed on liver and kidney samples, with ~30 samples for each organ (29 after QC). Results: Most dose-responsive pathways were common among chemicals/tissues, with the strongest effect on peroxisomal beta-oxidation. Effects on liver and kidney mitochondria-related pathways were notably unique to PCE. Tissue-specific acute transcriptional effects of TCE and PCE occurred at human equivalent doses comparable to those for apical effects. Conclusions: Our study is the first RNA-Seq transcriptional study of TCE vs. PCE in both liver and kidney, enabling a detailed comparison of the chemicals and effects on different organs. Our results show strong commonalities of effects, although PCE shows stronger transcriptional responses than TCE for the same equimolar doses.
2017-07-06 | GSE100296 | GEO
Project description:Trichloroethylene (TCE) is a widely used industrial chemical, and a common environmental contaminant. It is a well-known carcinogen in rodents and a probable carcinogen in humans. Studies utilizing panels of mouse inbred strains afford a unique opportunity to understand both metabolic and genetic basis for differences in responses to TCE. We tested the hypothesis that individual and liver-specific toxic effects of TCE are genetically controlled and that the mechanisms of toxicity and susceptibility can be uncovered by exploring responses to TCE using a diverse panel of inbred mouse strains. TCE (2100 mg/kg) or corn oil vehicle were administered by gavage to 6-8 wk old male mice of 15 mouse strains. Serum and liver were collected at 2, 8, and 24 hr post dosing and were analyzed for TCE metabolites, hepatocellular injury and gene expression of liver. TCE metabolism, as evident from the levels of individual oxidative and conjugative metabolites, varied considerably between strains. TCE treatment-specific effect on the liver transcriptome was strongly dependent on the individual’s genetic background. PPAR-mediated molecular networks, consisting of the metabolism genes known to be induced by TCE, represent some of the most pronounced molecular effects of TCE treatment in mouse liver that are dependent on the individual’s genetic background. Conversely, cell death, liver necrosis, and immune mediated response pathways which are affected by TCE treatment in liver are largely genetic background-independent. These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance.
2011-02-01 | GSE24278 | GEO
Project description:The industrial solvent trichloroethylene (TCE) produces a marked formic aciduria in male and female F344 rats and in male C57Bl mice following single or multiple dosing. The two major metabolites of TCE formed by cytochromes P450 metabolism also produce formic aciduria. The quantity of formic acid excreted was about 2-fold higher following trichloroacetic acid (TCA) compared to trichloroethanol (TCE-OH) or TCE, at similar doses of 16mg/kg/day for 3 days. Prior treatment of male F344 rats with 1-aminobenzotriazole a cytochrome P450 inhibitor, followed by TCE, completely prevented the formic aciduria but had no effect on formic acid excretion produced by TCA, suggesting TCA is the proximate metabolite producing this response. Metabolism of formic acid is largely controlled by the vitamin B12 –dependent methionine salvage pathway. Transcriptomic analysis on the liver of rats dosed with 16mg/kg/day TCE for three days when compared to control liver showed nine differentially expressed genes, of particular interest was the down regulation of LMBRD1 involved in the conversion of vitamin B12 into one of two molecules, methylcobalamin (CH3Cbl) or S-adenosylcobalamin (AdoCbl). Administration of CH3Cbl or hydroxocobalamin for 3 days to rats given a single dose of TCE, lead to a reduction in formic acid in their urine. Similarly, rats given TCE followed by L-methionine for 3 days excreted less formic acid in their urine. These findings suggest an effect on the vitamin B12 –dependent methionine salvage pathway. This was supported by the finding that hepatic methionine synthase, which converts homocysteine to methionine, was inhibited following three large daily dose of TCE. We propose that TCE metabolites interact with the vitamin B12 -dependent methionine salvage pathway leading to tetrahydrofolate deficiency and increased excretion of formic acid in rat urine.
2020-11-20 | GSE122664 | GEO
Project description:To examine changes, if any, in the expression of mRNAs in the liver tissue of mice, we have employed whole genome microarray expression profiling as a discovery platform to identify genes responsive to Trichloroethylene (TCE) treatment. In our results, the expression levels of 431 mRNAs were changed after TCE exposure, of which 291 were up-regulated and 140 were down-regulated. Using qPCR, we validated six of the mRNA expression changed genes, viz., Jun, Cdkn1a, Rad51b, Uhrf1, Svil and Ihh.
2014-11-14 | GSE58819 | GEO
Project description:Trichloroethylene (TCE) is primarily used as an industrial degreasing agent and has been in use since the 1940s. TCE is released into the soil, surface, and groundwater. From an environmental and regulatory standpoint more than half of Superfund hazardous waste sites on the National Priority List are contaminated with TCE. Occupational exposure to TCE occurs primarily via inhalation, while environmental TCE exposure also occurs through ingestion of contaminated drinking water. Current literature links TCE exposure to various adverse health effects including cardiovascular toxicity. Current studies aiming to address developmental cardiovascular toxicity utilized rodent and avian models with the majority of studies using relatively higher parts per million (ppm; mg/L) doses. In this study to further investigate developmental cardiotoxicity of TCE, zebrafish embryos were treated with 0, 10, 100, or 500 parts per billion (ppb; μg/L) TCE during embryogenesis and/or through early larval stages. After the appropriate exposure period, angiogenesis, F-actin polymerization, and mitochondrial function were assessed. A significant dose response decrease in angiogenesis, F-actin polymerization, and mitochondrial function was observed. To further complement this data, a transcriptomic profile of zebrafish larvae was completed to identify gene alterations associated with the 10 ppb TCE exposure. Results from the transcriptomic data revealed that an embryonic TCE exposure caused significant changes in genes associated with cardiovascular disease, cancer, and organismal injury and abnormalities with a number of targets in the FAK signaling pathway. Overall, results from our study further support TCE as a developmental cardiovascular toxicant and continued priority for environmental regulation.
2016-02-01 | GSE72918 | GEO
Project description:Wistar rats, male, treated with 500 mg/Kg/day of diacetyl by gavage, during 4 weeks
2018-04-18 | PXD004504 | Pride
Project description:Trichloroethylene (TCE) is an industrial solvent and widespread environmental contaminant. Human TCE exposure is prevalent, though epidemiological studies testing TCE exposure and adverse birth outcomes are inconclusive. The TCE metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) exhibits toxicity at human-relevant concentrations in a placental cell line. To date, DCVC cytotoxicity mechanistic studies have been limited to single molecular signaling pathways and biological responses. In the current study, genome-wide gene expression and gene set enrichment analyses (GSEA) were used to identify novel genes and pathways altered by human exposure-relevant DCVC concentrations in human placental villous explant tissues. The results of this study were compared to a parallel study using the placental cell line HTR-8/SVneo.
2021-03-16 | GSE154489 | GEO