2,3,7,8-Tetrachlorodibenzo-p-dioxin exposure disrupts development of the visceral and ocular vasculature

Aquat Toxicol. 2021 May:234:105786. doi: 10.1016/j.aquatox.2021.105786. Epub 2021 Feb 24.

Abstract

The aryl hydrocarbon receptor (AHR) has endogenous functions in mammalian vascular development and is necessary for mediating the toxic effects of a number of environmental contaminants. Studies in mice have demonstrated that AHR is necessary for the formation of the renal, retinal, and hepatic vasculature. In fish, exposure to the prototypic AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces expression of the AHR biomarker cyp1a throughout the developing vasculature and produces vascular malformations in the head and heart. However, it is not known whether the vascular structures that are sensitive to loss of AHR function are also disrupted by aberrant AHR activation. Here, we report that TCDD-exposure in zebrafish disrupts development of 1) the subintestinal venous plexus (SIVP), which vascularizes the developing liver, kidney, gut, and pancreas, and 2) the superficial annular vessel (SAV), an essential component of the retinal vasculature. Furthermore, we determined that TCDD exposure increased the expression of bmp4, a key molecular mediator of SIVP morphogenesis. We hypothesize that the observed SIVP phenotypes contribute to one of the hallmarks of TCDD exposure in fish - the failure of the yolk sac to absorb. Together, our data describe novel TCDD-induced vascular phenotypes and provide molecular insight into critical factors producing the observed vascular malformations.

Keywords: 2,3,7,8-Tetrachlorodibenzo-p-dioxin; Development; Dioxin; Gut; Kidney; Liver; Pancreas; Retina; SAV; SIVP; Subintestinal venous plexus; Superficial annular vessel; TCDD; Vascular development; Vasculature; Zebrafish.

MeSH terms

  • Animals
  • Animals, Genetically Modified / metabolism
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism
  • Liver / blood supply
  • Polychlorinated Dibenzodioxins / toxicity*
  • Retinal Vein / drug effects*
  • Retinal Vein / growth & development
  • Veins / drug effects
  • Water Pollutants, Chemical / toxicity*
  • Zebrafish / growth & development
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Bone Morphogenetic Protein 4
  • Polychlorinated Dibenzodioxins
  • Water Pollutants, Chemical
  • Zebrafish Proteins