title: Chronic sublethal exposure to silver nanoparticles disrupts thyroid hormone signaling during Xenopus laevis metamorphosis.
abstract: Nanoparticles (NPs) are engineered in the nanoscale (<100 nm) to have unique physico-chemical properties from their bulk counterparts. Nanosilver particles (AgNPs) are the most prevalent NPs in consumer products due to their strong antimicrobial action. While AgNP toxicity at high concentrations has been thoroughly investigated, the sublethal effects at or below regulatory guidelines are relatively unknown. Amphibian metamorphosis is mediated by thyroid hormone (TH), and initial studies with bullfrogs (Rana catesbeiana) indicate that low concentrations of AgNPs disrupt TH-dependent responses in premetamorphic tadpole tailfin tissue. The present study examined the effects of low, non-lethal, environmentally-relevant AgNP concentrations (0.018, 0.18 or 1.8 μg/L Ag; ∼10 nm particle size) on naturally metamorphosing Xenopus laevis tadpoles in two-28 day chronic exposures beginning with either pre- or prometamorphic developmental stages. Asymmetric flow field flow fractionation with online inductively coupled plasma mass spectrometry and nanoparticle tracking analysis indicated a mixture of single AgNPs with homo-agglomerates in the exposure water with a significant portion (∼30-40%) found as dissolved Ag. Tadpoles bioaccumulated AgNPs and displayed transient alterations in snout/vent and hindlimb length with AgNP exposure. Using MAGEX microarray and quantitative real time polymerase chain reaction transcript analyses, AgNP-induced disruption of five TH-responsive targets was observed. The increased mRNA abundance of two peroxidase genes by AgNP exposure suggests the presence of reactive oxygen species even at low, environmentally-relevant concentrations. Furthermore, differential responsiveness to AgNPs was observed at each developmental stage. Therefore, low concentrations of AgNPs had developmental stage-specific endocrine disrupting effects during TH-dependent metamorphosis.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 1700, STN CSC, Victoria, British Columbia, V8W 2Y2, Canada.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Carew
authors.affiliation: Water Quality Centre, Trent University, Peterborough, Ontario, K9J 7B8, Canada.
authors.forename: M Ehsanul
authors.initials: ME
authors.lastname: Hoque
authors.affiliation: Water Quality Centre, Trent University, Peterborough, Ontario, K9J 7B8, Canada.
authors.forename: Chris D
authors.initials: CD
authors.lastname: Metcalfe
authors.affiliation: Department of Chemistry, University of Montreal, C.P. 6128, succursale Centre-ville, Montreal, Québec, H3C 3J7, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Peyrot
authors.affiliation: Department of Chemistry, University of Montreal, C.P. 6128, succursale Centre-ville, Montreal, Québec, H3C 3J7, Canada.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wilkinson
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 1700, STN CSC, Victoria, British Columbia, V8W 2Y2, Canada. Electronic address: chelbing@uvic.ca.
authors.forename: Caren C
authors.initials: CC
authors.lastname: Helbing
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity; D004781:Environmental Exposure; D007814:Larva / Q000187:drug effects; D008675:Metamorphosis, Biological / Q000187:drug effects*; D053758:Nanoparticles / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*; D012834:Silver / Q000633:toxicity*; D013963:Thyroid Hormones / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity; D014982:Xenopus laevis / Q000254:growth & development / Q000502:physiology*
chemical_list: D052244:Endocrine Disruptors; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; D012834:Silver
keywords: Amphibian metamorphosis; Bioaccumulation; Microarray; Quantitative PCR; Silver nanoparticle; Thyroid hormone