Chronic sublethal exposure to silver nanoparticles disrupts thyroid hormone signaling during Xenopus laevis metamorphosis

Nanoparticles (NPs) are engineered in the nanoscale (<100nm) to have unique physico-chemical properties from their bulk counterparts. Nanosilver (nAg) is the most prevalent nanoparticle in consumer products due to its strong antimicrobial action. While nAg toxicity at high concentrations has been well described, the sublethal effects at or below regulatory guidelines are relatively unknown. Amphibian metamorphosis is mediated by thyroid hormone (TH), and initial studies indicate that low concentrations of nAg disrupt TH-dependent responses in precociously induced premetamorphic bullfrog (Rana catesbeiana) tadpoles. The present study examined the effects of environmentally-relevant nAg concentrations (LoAg, 0.018 µg/L; MedAg, 0.18 µg/L; HiAg, 1.8 µg/L) on naturally metamorphosing Xenopus laevis tadpoles in two 28-day chronic exposures beginning with pre- and prometamorphic stages, respectively. nAg was found to significantly bioaccumulate in tadpoles after 28 days. While nAg didn’t alter metamorphic timing, it increased hindlimb length during early premetamorphosis and in post-metamorphic juvenile tadpoles. Using MAGEX microarray and QPCR transcript analyses, 7 markers of nAg exposure were discovered and validated, 5 of which showed nAg-induced disruption of their TH-response. The increased mRNA abundance of two peroxidase genes suggests that nAg could generate reactive oxygen species (ROS) even at low, environmental concentrations. Furthermore, differential responsiveness to nAg was observed between developmental stages. Therefore, low concentrations of nAg had endocrine disruptive effects at both the physiological and molecular level, indicating that regulatory guidelines for silver may need revision. Six pre- or prometamorphic tadpoles were selected from each treatment and examined for the status of the hepatic transcriptome using MAGEX cDNA array analysis.