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Title: A rat toxicogenomics study with Calcium Sensitizer EMD 82571 reveals a pleiotropic cause in teratogenicity      
dateReleased:
01-16-2014
description:
The aim of reprotoxicity testing is to reveal adverse effects of chemicals and drugs on reproduction and on pre and postnatal fetal development. There is very limited data available on gene expression profiling for elucidation of the teratogenic effects of nongenotoxic teratogens. Therefore, research was undertaken to obtain knowledge on the molecular effects of MSC1096199 (previously known as EMD 82571), a calcium sensitizer that was abandoned in the preclinical development phase due to its teratogenic effects in some foetuses. Pregnant wistar rats were dose daily with either MSC1096199 (50 or 150 mg/kg) or Retinoic acid (10 mg/kg) on gestational days 6-17. Microarray experiment were performed using four different tissues (maternal liver, embryo liver (GD20), embryo bone (GD20), and whole embryo (GD12)) under four different conditions (vehicle, low dose and high dose of MSC1096199 and Retinoic acid) to determine the drug regulated genes. In the high dose treatment group, approximately 58% of the fetuses showed malformations i.e. exencephaly and agnathia, and toxicogenomics evidenced that the genes critically involved in osteogenesis, odontogenesis and extra cellular matrix components to be significantly regulated by MSC1096199, therefore providing a molecular rational for the observed teratogenic effects. Two-condition experiment, RA vs EMD 82571. Biological replicates:5 control, 5 treated. RNA from control and treatment groups were labeled with Cy3 and Cy5 fluorochromes, respectively. Cy3-channel pictures and correspondig raw data files are marked as 1b. Cy5-channel pictures and correspondig raw data files are marked as 2b.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-54121
refinement:
raw
alternateIdentifiers:
54121
keywords:
functional genomics
dateModified:
05-04-2014
availability:
available
types:
gene expression
name:
Rattus norvegicus
ID:
A-GEOD-18176
name:
Rat teratogenicity custom array
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-54121/E-GEOD-54121.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-54121/E-GEOD-54121.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54121
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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