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.
A rat toxicogenomics study with the calcium sensitizer EMD82571 reveals a pleiotropic cause of teratogenicity.
Specimen part, Treatment
View SamplesWe report a gene expression changes during development and maturation of the murine utricle Overall design: Using RNA-sequencing, we examined the gene expression in the murine utricle at E17.5, p0, and p9
SoxC transcription factors are essential for the development of the inner ear.
Specimen part, Cell line, Subject
View Sampleswe evaluated the mechanism behind NOTCH activation in prostate cancer
Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence.
Specimen part
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