2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in the zebrafish embryo: altered regional blood flow and impaired lower jaw development

Teraoka, H., Dong, W., Ogawa, S., Tsukiyama, S., Okuhara, Y., Niiyama, M., Ueno, N., Peterson, R.E., and Hiraga, T.
Toxicological sciences : an official journal of the Society of Toxicology   65(2): 192-199 (Journal)
Registered Authors
Dong, Wu, Peterson, Richard E., Teraoka, Hiroki, Ueno, Naoto
Ah receptor (AhR); 2,3,7,8-tetrachlorodibenzo-p-dioxin; (TCDD); zebrafish; embryo; developmental toxicity; craniofacial; jaw; cardiovascular; blood flow; cartilage
MeSH Terms
  • Animals
  • Dose-Response Relationship, Drug
  • Embryonic and Fetal Development/drug effects*
  • Environmental Pollutants/toxicity*
  • In Situ Hybridization
  • Jaw/blood supply
  • Jaw/drug effects*
  • Jaw/embryology
  • Jaw Abnormalities/chemically induced*
  • Microscopy, Video
  • RNA, Messenger/metabolism
  • Receptors, Aryl Hydrocarbon/biosynthesis
  • Receptors, Aryl Hydrocarbon/genetics
  • Regional Blood Flow/drug effects*
  • Videotape Recording
  • Zebrafish
11812923 Full text @ Toxicol. Sci.
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on regional red blood cell (RBC) perfusion rate, as an index of blood flow, and lower jaw development were investigated quantitatively in zebrafish embryos (Danio rerio) during early development. As revealed by observation of live embryos and alcian-blue staining, TCDD retarded lower jaw development in a concentration-dependent manner with only a minor inhibitory effect on total body length. Both inhibitory effects were significant as early as 60 h postfertilization (hpf), at which time the area of goosecoid (gsc) mRNA expression was clearly reduced in the lower jaw. To examine effects of TCDD on RBC perfusion rate, time-lapse recording was performed using a digital video camera attached to a light microscope. TCDD did not show marked effects on RBC perfusion rate until 72 hpf, when vessel-specific effects emerged. TCDD severely inhibited RBC perfusion rate in intersegmental arteries of the trunk, but only modestly and slightly inhibited RBC perfusion rate in certain vessels of the head such as the central arteries and optic vein. Conversely, at both 72 and 84 hpf, TCDD significantly increased RBC perfusion rate in the hypobranchial artery branching to the lower jaw primordia, and then reduced it at 96 hpf. RBC perfusion rate in all vessels examined in TCDD-exposed embryos was inhibited at 96 hpf. The zebrafish aryl hydrocarbon receptor 2 (zfAhR2) mRNA was strongly expressed in the lower jaw primordia at 48 hpf, and expression of this transcript was augmented by TCDD treatment. Thus, TCDD exposure of the zebrafish embryo has a disruptive effect on local circulation and lower jaw cartilage growth. Initially, TCDD may act directly on the lower jaw primordia to impair lower jaw development. Reductions in hypobranchial RBC perfusion rate occurred well after the initial retardation in lower jaw development had become apparent, and may contribute further to the effect.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes