title: Gold nanoparticles disrupt zebrafish eye development and pigmentation.
abstract: Systematic toxicological study is still required to fully understand the hazard potentials of gold nanoparticles (AuNPs). Because their biomedical applications are rapidly evolving, we investigated developmental toxicity of AuNPs in an in vivo embryonic zebrafish model at exposure concentration ranges from 0.08 to 50mg/l. Exposure of zebrafish embryos to 1.3 nm AuNPs functionalized with a cationic ligand, N,N,N-trimethylammoniumethanethiol (TMAT-AuNPs), resulted in smaller malpigmented eyes. We determined that TMAT-AuNPs caused a significant increase of cell death in the eye, which was correlated with an increase in gene expression of p53 and bax. Expression patterns of key transcription factors regulating eye development (pax6a, pax6b, otx2, and rx1) and pigmentation (sox10) were both repressed in a concentration-dependent manner in embryos exposed to TMAT-AuNPs. Reduced spatial localization of pax6a, rx1, sox10, and mitfa was observed in embryos by whole-mount in situ hybridization. The swimming behavior of embryos exposed to sublethal concentrations of TMAT-AuNPs showed hypoactivity, and embryos exhibited axonal growth inhibition. Overall, these results demonstrated that TMAT-AuNPs disrupt the progression of eye development and pigmentation that continues to behavioral and neuronal damage in the developing zebrafish.
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Kim
authors.forename: Tatiana
authors.initials: T
authors.lastname: Zaikova
authors.forename: James E
authors.initials: JE
authors.lastname: Hutchison
authors.forename: Robert L
authors.initials: RL
authors.lastname: Tanguay
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D005123:Eye / Q000187:drug effects* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006046:Gold; D017403:In Situ Hybridization; D053768:Metal Nanoparticles / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000196:embryology; D013550:Swimming; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; D051028:bcl-2-Associated X Protein; C571228:tp53 protein, zebrafish; D006046:Gold
keywords: behavior; eye defect; gold nanoparticles; neuronal toxicity; pigmentation; zebrafish.
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