PUBLICATION
Developmental exposure to BDE-99 hinders cerebrovascular growth and disturbs vascular barrier formation in zebrafish larvae
- Authors
- Zhong, X., Kang, J., Qiu, J., Yang, W., Wu, J., Ji, D., Yu, Y., Ke, W., Shi, X., Wei, Y.
- ID
- ZDB-PUB-190701-31
- Date
- 2019
- Source
- Aquatic toxicology (Amsterdam, Netherlands) 214: 105224 (Journal)
- Registered Authors
- Keywords
- Cerebrovasculature, Developmental toxicity, Polybrominated diphenyl ethers, Vascular barrier, Vascular toxicity, Zebrafish
- MeSH Terms
-
- Animals
- Blood Vessels/drug effects*
- Brain/blood supply
- Brain/growth & development
- Capillary Permeability/drug effects
- Environmental Exposure*
- Gene Expression Regulation, Developmental/drug effects
- Halogenated Diphenyl Ethers/toxicity*
- Inflammation/genetics
- Inflammation/pathology
- Larva/drug effects
- Neovascularization, Physiologic/drug effects
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Tight Junctions/drug effects
- Tight Junctions/metabolism
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Vascular Endothelial Growth Factor Receptor-2/genetics
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Water Pollutants, Chemical/toxicity
- Zebrafish/genetics
- Zebrafish/growth & development*
- PubMed
- 31255847 Full text @ Aquat. Toxicol.
Citation
Zhong, X., Kang, J., Qiu, J., Yang, W., Wu, J., Ji, D., Yu, Y., Ke, W., Shi, X., Wei, Y. (2019) Developmental exposure to BDE-99 hinders cerebrovascular growth and disturbs vascular barrier formation in zebrafish larvae. Aquatic toxicology (Amsterdam, Netherlands). 214:105224.
Abstract
Polybrominated diphenyl ethers (PBDEs) are distributed throughout the environment. Despite a moratorium on their use, concentrations of PBDEs in the atmosphere and in residential environments remain high due to their persistence. The environmental health risks remain concerning and one of the major adverse effects is neurodevelopmental toxicity. However, the early response and effects of PBDEs exposure on the developing brain remain unknown. In the present study, we investigated the impacts of 2,2',4,4',5-pentabrominated diphenyl ether (BDE-99) on vascular growth and vascular barrier function with an emphasis on cerebral blood vessels, in the early life stages, using a zebrafish model. No general toxicity was observed in exposing zebrafish larvae to 0-0.5 μM BDE-99 at 72 hpf. BDE-99 exposure resulted in neither general toxicity nor pronounced developmental impairment in somatic blood vessels, including intersegmental vessels (ISV) and common cardinal veins (CCV). Meanwhile, both 0.05 μM and 0.5 μM of BDE-99 reduced cerebrovascular density as well as down-regulation of VEGFA and VEGFR2 in the head. In addition, BDE-99 exposure increased vascular leakage, both in cerebral and truncal vasculature at 72 hpf. The accentuated vascular permeability was observed in the head. The mRNA levels of genes encoding tight junction molecules decreased in the BDE-99-exposed larvae, and more robust reductions in Cldn5, Zo1 and Jam were detected in the head than in the trunk. Moreover, proinflammatory factors including TNF-α, IL-1β and ICAM-1 were induced, and the expression of neurodevelopment-related genes was suppressed in the head following BDE-99 exposure. Taken together, these results reveal that developmental exposure to BDE-99 impedes cerebrovascular growth and disturbs vascular barrier formation. The cerebral vasculature in developing zebrafish, a more sensitive target for BDE-99, may be a promising tool for the assessment of the early neurodevelopmental effects due to PBDEs exposure.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping