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Rattus norvegicus

ABSTRACT: A rat toxicogenomics study with Calcium Sensitizer EMD 82571 reveals a pleiotropic cause and adverse outcome pathway of teratogenicity



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A rat toxicogenomics study with the calcium sensitizer EMD82571 reveals a pleiotropic cause of teratogenicity.

Hewitt Philip G PG   Singh Prafull Kumar PK   Kumar Arun A   Gnewuch Carsten C   Liebisch Gerhard G   Schmitz Gerd G   Borlak Juergen J  

Reproductive toxicology (Elmsford, N.Y.) 20140628

The calcium sensitizer and PDEIII inhibitor EMD82571 caused exencephaly, micrognathia, agnathia and facial cleft in 58% of fetuses. In pursue of mechanisms and to define adverse outcome pathways pregnant Wistar rats were dosed daily with either EMD82571 (50 or 150mg/kg/day) or retinoic acid (12mg/kg/day) on gestational days 6-11 and 6-17, respectively. Hypothesis driven and whole genome microarray experiments were performed with whole embryo, maternal liver, embryonic liver and malformed bone at  ...[more]

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