Combining mouse embryonic stem cells and zebrafish embryos to evaluate developmental toxicity of chemical exposure.

ABSTRACT

The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish embryos to evaluate the potential developmental toxicity of industrial and pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo teratogenicity were tested in the assays and correlations to mammalian data. Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals were measured. In zebrafish embryos, lethality and the lowest effect level concentrations for morphological malformations were determined. Clustering of the assays based on frequency of affected assays resulted in a ranking of the test compounds that correlated to in vivo rodent data (R = 0.88, P < 0.001). We conclude that the combination of ESC- and zebrafish-based assays provides a valuable platform for the prioritization of pharmaceutical and industrial chemicals for further testing of developmental toxicity in rodents.