Non-cytotoxic silver nanoparticle levels perturb human embryonic stem cell-dependent specification of the cranial placode in part via FGF signaling

Abstract

Silver nanoparticles (AgNPs) are compounds used in numerous consumer products because of their desirable optical, conductive and antibacterial properties. However, several in vivo and in vitro studies have raised concerns about their potential developmental toxicity. Here, we employed a human embryonic stem cell model to evaluate the potential ectodermal toxicity of AgNPs, at human relevant concentrations. Among the four major ectodermal lineages tested, only cranial placode specification was significantly affected by AgNPs and AgNO₃, morphology-wise and in the expression of specific markers, such as SIX3 and PAX6. Mechanistically, we found that the effects of AgNPs on the cranial placode differentiation were probably due to Ag ion leakage and mediated by the FGF signaling. Thus, AgNPs may have the ability to alter the early stages of embryonic development.

Keywords: Cranial placode; Developmental toxicity; Ectoderm; Silver nanoparticles (AgNPs); Stem cell toxicology.