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| Status |
Public on Jun 07, 2014 |
| Title |
A rat toxicogenomics study with Calcium Sensitizer EMD 82571 reveals a pleiotropic cause and adverse outcome pathway of teratogenicity |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
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 (12 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.
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| Overall design |
Pregnant wistar rats were treated daily with the dose of either MSC1096199 (50 or 150 mg/kg) or Retinoic acid (12 mg/kg) on gestational days 6-17. Microarray experiment were performed using four different tissues (maternal liver, embryo liver, embryo bone, and whole embryo) under four different conditions (vehicle, low dose and high dose of MSC1096199 and Retinoic acid) to determine the drug regulated genes.
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| Contributor(s) |
Borlak J, Singh PK, Kumar A |
| Citation(s) |
24977338 |
| Submission date |
Jun 04, 2014 |
| Last update date |
Mar 03, 2017 |
| Contact name |
Juergen Borlak |
| E-mail(s) |
Borlak.Juergen@mh-hannover.de
|
| Phone |
+49 511 532 7249
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| Organization name |
Hannover Medical School
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| Department |
Centre for Pharmacology and Toxicology
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| Lab |
Institute of Pharmaco- and Toxicogenomics
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| Street address |
Feodor-Lynen-Str. 35
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| City |
Hannover |
| State/province |
Lower Saxony |
| ZIP/Postal code |
30625 |
| Country |
Germany |
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| Platforms (1) |
| GPL341 |
[RAE230A] Affymetrix Rat Expression 230A Array |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA251867 |
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