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E-GEOD-20952 - Discriminating reprotoxic and non-reprotoxic phthalates by transcriptomics analysis of rat testis

Status
Released on 31 August 2010, last updated on 2 March 2012
Organism
Rattus norvegicus
Samples (52)
Array (1)
Protocols (8)
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.
Experiment type
transcription profiling by array 
Contacts
Xiaolian Yuan <x.yuan@uva.nl>, Aart Verhoef, Betty C Hakkert, Floyd R Wittink, Harry van Steeg, Jan van Benthem, Jillian de Wilde, Jos G Bessems, Martijs J Jonker, Mirjam Luijten, Raoul Kuiper, Timo M Breit
Citation
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-20952.idf.txt
Sample and data relationshipE-GEOD-20952.sdrf.txt
Raw data (2)E-GEOD-20952.raw.1.zip, E-GEOD-20952.raw.2.zip
Processed data (1)E-GEOD-20952.processed.1.zip
Array designA-GEOD-10226.adf.txt
R ExpressionSetE-GEOD-20952.eSet.r
Links