Increased coiling frequency linked to apoptosis in the brain and altered thyroid signaling in zebrafish embryos (Danio rerio) exposed to the PBDE metabolite 6-OH-BDE-47.


Polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants that are ubiquitously detected in the environment and associated with adverse health outcomes. 6-OH-BDE-47 is a metabolite of the flame retardant, 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), and there is increasing concern regarding its developmental neurotoxicity and endocrine disrupting properties. In this study, we report that early life exposure in zebrafish (Danio rerio) embryos to 6-OH-BDE-47 (50 and 100 nM) resulted in higher coiling frequency and significantly increased apoptotic cells in the brain. These effects were partially rescued by overexpression of thyroid hormone receptor β (THRβ) mRNA. Moreover, exposure to 100 nM 6-OH-BDE-47 significantly reduced the number of hypothalamic 5-hydroxytryptamine (5-HT, serotonin)-immunoreactive (5-HT-ir) neurons and the mRNA expression of tryptophan hydroxylase 2 (TPH2). These results indicate that 6-OH-BDE-47 affected thyroid hormone regulation through THRβ and negatively impacted the nervous system, in turn, affecting coiling behavior. Correlations of these endpoints suggest that coiling frequency could be used as an indicator of neurotoxicity in embryos.





Published Version (Please cite this version)


Publication Info

Wang, Feng, Mingliang Fang, David E Hinton, Melissa Chernick, Shenglan Jia, Yingdan Zhang, Lingtian Xie, Wenjing Dong, et al. (2018). Increased coiling frequency linked to apoptosis in the brain and altered thyroid signaling in zebrafish embryos (Danio rerio) exposed to the PBDE metabolite 6-OH-BDE-47. Chemosphere, 198. pp. 342–350. 10.1016/j.chemosphere.2018.01.081 Retrieved from

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.



David E. Hinton

Nicholas Distinguished Professor Emeritus of Environmental Quality

The Hinton laboratory focuses on mechanistic toxicity in all life stages of small, aquarium model fish and in selected species with particular environmental relevance (freshwater and marine). With the latter, investigations focus on stressor responses and include follow up studies after oil spills. Studies with the laboratory model fish take advantage of the compressed life cycle to improve understanding of organellar, cellular and tissues responses that arise after exposure and follow either a temporal and/or a concentration gradient. At the end of these serial examinations, we have pioneered the use of high resolution light and fluorescent microscopy and electron microscopy in these small fish species to better understand resultant phenotypes and to correlate structural alteration with molecular biological studies. In this way we are anchoring phenotypes with gene expression. In individual fish where specific genes have been mutated (Collaboration with Dr. Keith Cheng, Hershey Medical Center, Hershey, PA) or in individuals exposed to organic substances of known or expected toxicity, structural analysis at various levels of biological organization enables integration across all levels of biological organization enabling whole body phenomics. Special projects include The Duke Superfund Research Center, 2P42-ESO10356-10A2, supported by NIH/NIEHS. Studies investigate responses of fish to polycyclic aromatic hydrocarbons and include early life stages and multigenerational effects. Contaminated and reference sites are included in these investigations of feral fish. Also, we receive funding as part of theme 2 of the Center for Environmental Implications of Nano Technology (CEINT). Our studies seek to determine whether there are specific toxic consequences upon exposure to nano silver (Ag NPs) versus exposure to conventional silver. We hosted Na Zheng (Angie), Visiting Investigator, Associate Professor, Northeast Institute of Geography and Agricultural Ecology, Chinese Academy of Sciences. She was the recipient of a K.C. Wong award supporting her role as visiting investigator. Together, we investigated metals mixtures and embryo toxicity. We collaborate with Stella Marinakos, Pratt School and CEINT on the synthesis and refinement of nanoselenium. This complements work done over the past year with seleno-methionine and sodium selenite in parental and embryo exposures. We continue to investigate ways to assess whole body responses of aquarium model fish and to link phenotype to genotype. Collaboration with the Stapleton laboratory has investigated alterations in embryo and larval zebrafish exposed to flame retardant compounds and selected metabolites. Here our morphologic investigations have helped to differentiate between delayed development and toxicity in the developing eye.

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.