PUBLICATION
Developmental toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the potential role of thyroid receptor β
- Authors
- Macaulay, L.J., Chen, A., Rock, K.D., Dishaw, L.V., Dong, W., Hinton, D.E., Stapleton, H.M.
- ID
- ZDB-PUB-151005-1
- Date
- 2015
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 168: 38-47 (Journal)
- Registered Authors
- Dong, Wu
- Keywords
- Development, Metabolite, OH-BDE, PBDE, Thyroid receptor, Zebrafish
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/drug effects*
- Polybrominated Biphenyls/toxicity*
- Thyroid Gland/drug effects
- Thyroid Hormone Receptors beta/metabolism*
- Thyroid Hormones/metabolism
- Triiodothyronine/metabolism
- Water Pollutants, Chemical/toxicity
- Zebrafish/physiology*
- PubMed
- 26433919 Full text @ Aquat. Toxicol.
- CTD
- 26433919
Citation
Macaulay, L.J., Chen, A., Rock, K.D., Dishaw, L.V., Dong, W., Hinton, D.E., Stapleton, H.M. (2015) Developmental toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the potential role of thyroid receptor β. Aquatic toxicology (Amsterdam, Netherlands). 168:38-47.
Abstract
6-hydroxy-2,2',4,4'-tetrabromodiphenyl ether (6-OH-BDE-47) is both a polybrominated diphenyl ether (PBDE) flame retardant metabolite and a marine natural product. It has been identified both as a neurotoxicant in cell-based studies and as a developmental toxicant in zebrafish. However, hydroxylated PBDE metabolites are also considered thyroid hormone disruptors due to their structural similarity to endogenous thyroid hormones. The purpose of this study was to evaluate the effects of 6-OH-BDE-47 on a developmental pathway regulated by thyroid hormones in zebrafish. Morphological measurements of development (head trunk angle, otic vesicle length, and eye pigmentation) were recorded in embryos at 30h post fertilization (hpf) and detailed craniofacial morphology was examined in 4 day old larvae using cartilage staining. Exposure to 6-OH-BDE-47 resulted in severe developmental delays. A 100nM concentration resulted in a 26% decrease in head trunk angle, a 54% increase in otic vesicle length, and a 42% decrease in eye pigmentation. Similarly, altered developmental morphology was observed following thyroid receptor β morpholino knockdown, exposure to the thyroid hormone triiodothyronine (T3) or to thyroid disrupting chemicals (TDC; iopanoic acid and propylthiouracil). The threshold for lower jaw deformities and craniofacial cartilage malformations was at doses greater than 50nM. Of interest, these developmental delays and effects were rescued by microinjection of TRβ mRNA during the 1-2 cell stage. These data indicate that OH-BDEs can adversely affect early life development of zebrafish and suggest they may be impacting thyroid hormone regulation in vivo through downregulation of the thyroid hormone receptor.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping