Cellular and molecular basis of cadmium‐induced deformities in zebrafish embryos

Abstract

AbstractCadmium is known to cause developmental defects in a varietyof vertebrate species, but relatively little is known about the underlying molecular mechanisms. In this study, we used zebrafish (Danio rerio) embryos as a model system to investigate cadmium‐induced toxicities. Fertilized embryos collected at 5‐h after fertilization were incubated for 18 h in culture media containing 1 to 1, 000 μM CdCl2. The median embryolethal concentration (LC50) was 168 μM, whereas the median effect concentration (EC50) for total adverse effect (mortality and developmental defects) was 138 μM. Six major types of deformities were observed: head and eye hypoplasia, hypopigmentation, cardiac edema, yolk sac abnormalities, altered axial curvature, and tail malformations. The frequency of malformations increased with cadmium concentration. Somites of embryos with altered axial curvature were investigated using the antimyosin antibody MF‐20. This study demonstrated, to our knowledge for the first time, reduced myotome formation in cadmium‐induced spinal deformity. Embryos with head and eye hypoplasia were studied using the anti‐neural tissue antibody zns‐2, and a poorly developed central nervous system was revealed. Head and eye hypoplasia were associated with lack of expression of the sonic hedgehog gene, which controls the patterning of the neural tube and somites. Genes involved in tail formations, such as evenskipped 1 and no tail, were ectopically expressed in embryos with tail malformations. Our data support the hypothesis that fish embryonic malformations induced by cadmium might be mediated through ectopic expression of developmental regulatory genes.