Arsenic impairs embryo development via down-regulating Dvr1 expression in zebrafish.

Exposure to environmental inorganic arsenic compounds has serious health effects on humans, including cancer, cardiovascular disease, developmental and reproductive problems. Our previous study showed that arsenic exposure caused various signs of toxicity in early stages of zebrafish development, including cardiac and neural system, such as pericardium edema, circulation failure, heart malformation. However, how arsenic exerts these effects is little known. Here, real-time quantitative RT-PCR and whole-mount in situ hybridization data showed that zebrafish Dvr1, a mammalian homolog of GDF1 related to the formation of left-right axis, was significantly down-regulated in embryos exposed to arsenite. Embryos with Dvr1 knockdown by antisense morpholino displayed abnormal development, including pericardium edema and failed looping, which is similar to the defects phenotype with arsenic treatment. Furthermore, overexpression of GDF1 significantly rescued development anomalies caused by morpholino or arsenite. Taken together, our results indicated for the first time that Dvr1 played an important role in the left-right asymmetry establishment of zebrafish embryo, and Dvr1 was involved in arsenic-mediated embryo toxicity, which gives novel insight into molecular mechanism of arsenic-mediated embryo toxicity.