Mechanisms of silver_nanoparticles induced hypopigmentation in embryonic zebrafish

Silver_nanoparticles (AgNPs) have been reported to inhibit specification of erythroid cells and to induce spinal cord deformities and cardiac arrhythmia in vertebrates, but have not been implicated in development of neural crest (NC) and pigment cells in an in vivo model yet. In current study, down-regulated expressions of NC genes pax7 and foxd3, melanophore genes mitfa and dct, and xanthophore gene gch2 in AgNPs-exposed embryos were revealed by microarray, qRT-PCR and whole-mount in situ hybridization (WISH). Then, the down-regulated expressions of melanophore genes mitfa and dct but not xanthophore gene gch2 in AgNPs-exposed embryos were found to be recovered by melanogenesis agonists palmitic acid and dibutyryl cyclic AMP (dbcAMP). Finally, Ag⁺ chelating and AgNPs coating compound l-cysteine was found to neutralize AgNPs-induced hypopigmentation in AgNPs-exposed embryos, and to recover the down-regulated expressions of both dct and gch2 to nearly normal level in embryos, suggesting that AgNPs-releasing Ag⁺ might mediate their biological effects on zebrafish pigmentation mostly. This study was firstly to unveil that AgNPs might specifically act up-stream of mitfa and pax7 genes to suppress specification and differentiation of melanophore and xanthophore lineages respectively by their releasing Ag⁺ during vertebrate embryogenesis.