l-selenomethionine induces zebrafish embryo cardiovascular defects via down-regulating expression of lrp2b.

Selenium plays crucial roles in maintaining the growth and development of vertebrates including humans. However, excessive selenium in cells will lead to developmental defects and disease. Selenium has been reported to cause severe malformation in zebrafish embryos, but there are few studies on the mechanism of selenium excess-induced cardiovascular defects. In this study, the fertilized zebrafish embryos were treated with selenium for 96 h post fertilization (hpf). Under selenium stress, wild-type embryos showed pericardial edema, heart rate decrease, ectopic accumulation of hemoglobin; fli1-eGFP transgenic zebrafish displayed intersegmental vessel injury; and myl7-eGFP transgenic zebrafish exhibited atrial area increase. RNA-seq data and qRT-PCR results indicated that the expressions of cardiovascular development genes were up-regulated in selenium-stressed embryos. The expressions of lipid metabolism-related and selenium metabolism-related genes were evaluated in embryos. Among the tested genes, the expression of lrp2b was down-regulated in both 24 hpf and 96 hpf embryos. Furthermore, lrp2b-knockdown embryos exhibited the cardiac defects similar to selenium-stress embryos, and the over-expression of lrp2b rescued the selenium-induced defects, indicating that lrp2b might play a key role in regulating selenium cardiotoxicity. In summary, our research evaluates the cardiotoxicity of excessive selenium, and reveals the molecular mechanism of cardiovascular defects in selenium-exposed zebrafish embryos.