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Discriminating reprotoxic and non-reprotoxic phthalates by transcriptomics analysis of rat testis

ABSTRACT: REACH, the EU regulation on chemicals and their safe use, stipulates that about 30,000 chemical substances are to be assessed on their possible risks. Toxicological evaluation of these compounds will at least partly be based on animal testing. Especially reproductive toxicity is one of the most complicated, time-consuming and expensive in vivo endpoints. Introducing microarray-based endpoints can potentially refine in vivo toxicity testing. If compounds from a distinct chemical class induce reproducible gene-expression responses with a recognizable overlap, these gene-expression signatures may indicate intrinsic features of certain compounds, including toxicity. In the present study, we investigated this theory for the reproductive toxicity of phthalates. Male rats were treated with a single dose of either reprotoxic or non-reprotoxic phthalates and sacrificed 24h thereafter. Subsequently, histopathological and gene-expression profiling analyses were performed. Despite ambiguous histopathological observations, we were able to distinguish the reprotoxic from the non-reprotoxic phthalates based on differential gene expression. This shows that differences in gene expression indicative for the type of exposure can be detected earlier, or at lower doses, than phenotypic tissue damage. These findings are promising for ’early warning’ biomarker analyses and for using toxicogenomics in a category approach.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE20952 | GEO | 2010/09/01

SECONDARY ACCESSION(S): PRJNA124439

REPOSITORIES: GEO

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Discriminating reprotoxic and non-reprotoxic phthalates by transcriptomics analysis of rat testis

Project description:REACH, the EU regulation on chemicals and their safe use, stipulates that about 30,000 chemical substances are to be assessed on their possible risks. Toxicological evaluation of these compounds will at least partly be based on animal testing. Especially reproductive toxicity is one of the most complicated, time-consuming and expensive in vivo endpoints. Introducing microarray-based endpoints can potentially refine in vivo toxicity testing. If compounds from a distinct chemical class induce reproducible gene-expression responses with a recognizable overlap, these gene-expression signatures may indicate intrinsic features of certain compounds, including toxicity. In the present study, we investigated this theory for the reproductive toxicity of phthalates. Male rats were treated with a single dose of either reprotoxic or non-reprotoxic phthalates and sacrificed 24h thereafter. Subsequently, histopathological and gene-expression profiling analyses were performed. Despite ambiguous histopathological observations, we were able to distinguish the reprotoxic from the non-reprotoxic phthalates based on differential gene expression. This shows that differences in gene expression indicative for the type of exposure can be detected earlier, or at lower doses, than phenotypic tissue damage. These findings are promising for ’early warning’ biomarker analyses and for using toxicogenomics in a category approach. Male rats were treated with a single dose of either reprotoxic (DMP, DEP, DPrP, DOP) or non-reprotoxic phthalates (DBP, DPeP, DHP, DEHP, MEHP), positive control (2-ME) or negative control (vehicle) and killed 24 h thereafter. Rat testes were preserved for RNA extraction and hybridization on Affymetrix microarrays.

2010-08-31 | E-GEOD-20952 | biostudies-arrayexpress

Evaluation of 5-Day In Vivo Rat Liver and Kidney with High-Throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes

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Comparative Time Course Profiles of Phthalate Stereoisomers in Mice

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Using transcriptomics and metabolomics to understand species differences in sensitivity to chlorpyrifos in Japanese quail and double-crested cormorant embryos

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2021-07-15 | GSE179770 | GEO

Transcriptional profile of the liver of zebrafish after feeding with 0% or 25% dietary maize substitution

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Exploring gene expression dynamics in zebrafish embryos exposed to trenbolone: A 96-Hour RNA-seq Study

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2024-08-31 | E-MTAB-14032 | biostudies-arrayexpress

Rattus norvegicus

Project description:Mechanistic evaluation of the insulin response in H4IIE hepatoma cells: New endpoints for toxicity testing?

| PRJNA152033 | ENA

Role of PPARalpha in the effects of DEHP on the hepatic expression of a selection of mouse genes

Project description:Role of PPARalpha in the effects of DEHP on the hepatic expression of a selection of mouse genes related to nuclear receptor signaling. Di-(2-ethylhexyl)-phthalate (DEHP), a widely used plasticizer, is detected in consumer’s body fluids. Contamination occurs through environmental and food chain sources. In mouse liver, DEHP activates the peroxisome proliferator-activated receptor alpha (PPARalpha) and regulates the expression of its target genes. Several in vitro investigations support the simultaneous recruitment of additional nuclear receptor pathways. We investigated, in vivo, the hepatic impact of low doses of DEHP on PPARalpha activation, and the putative activation of additional signalling pathways. Wild-type and PPARalpha-deficient mice were exposed to different doses of DEHP. Gene expression profiling delineated the role of PPARalpha and revealed a PPARalpha-independent regulation of several prototypic Constitutive Androstane Receptor (CAR) target genes. This finding demonstrates that CAR also represents a transcriptional regulator sensitive to phthalates. CAR-mediated effects of DEHP provide a new rationale for most endpoints of phthalates toxicity described previously, including endocrine disruption, hepatocarcinogenesis and the metabolic syndrome. Keywords: Treatment effect

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