Regular Article
Hemodynamic Dysfunction and Cytochrome P4501A mRNA Expression Induced by 2,3,7,8-Tetrachlorodibenzo-p-dioxin during Embryonic Stages of Lake Trout Development

https://doi.org/10.1006/taap.2000.8999Get rights and content

Abstract

Lake trout embryos exposed to [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) manifest toxicity after hatching by subcutaneous edema of the yolk sac, pericardial edema, meningeal edema, subcutaneous hemorrhages, and a marked congestion of blood flow in various vascular beds culminating in death. Our objective was to determine if this syndrome was associated temporally with morphologic lesions in the vascular endothelium, increased vascular permeability, and cytochrome P4501A (CYP1A) mRNA induction. Lake trout embryos exposed as fertilized eggs to TCDD were found to exhibit marked reductions in perfusion of the peripheral vasculature during the early sac fry stage of development (stage F19), which consistently preceded other gross lesions and mortality observed later in sac fry development (stage F210). This reduction in blood flow was manifested as severe capillary congestion and hemoconcentration in certain vascular beds. Transmission electron microscopic (TEM) examination of endothelial cells in these vascular beds failed to reveal cellular necrosis at hatching (stage E58) and throughout sac fry development (stages F19–F210). Rather, only subtle ultrastructural changes in endothelial cells were found consisting of increased vacuolation, separation of intercellular junctions, and cytoplasmic blebbing, consistent with the TCDD dose and time course for developmental cardiovascular toxicity, which began to manifest itself in some embryos approximately 1 week prior to hatching (E58). To assess permeability of yolk sac vasculature to certain constituents in blood, sac fry (stage F210) were analyzed for the presence of plasma proteins, granulocytes, and serum creatine kinase activity in yolk sac subcutaneous edema fluid from control and TCDD-exposed treatment groups. TCDD dose- and time-related increases in yolk sac edema volume, plasma protein content of edema fluid, granulocyte concentration, and creatine kinase activity in the fluid were observed in midstage and late stage of sac fry development (stage F210). Thus, yolk sac subcutaneous edema fluid is an ultrafiltrate of blood and results from increased vascular permeability. In contrast to the changes in vascular blood flow and permeability induced by TCDD during stages F19 and F210 of sac fry development, respectively, CYP1A mRNA levels were induced by TCDD as early as the 10-somite embryo (stage E25). TCDD also caused a dose-related increase in CYP1A mRNA levels in sac fry at hatching (stage E58) and throughout sac fry development (stages F19–F210). We conclude that subtle, ultrastructural changes in vascular endothelial cells consistently precede increases in vascular permeability and sac fry mortality; however, induction of CYP1A mRNA occurs prior to any observable morphological lesions, changes in vascular permeability, or sac fry mortality.

References (63)

  • M.E. Hahn et al.

    The Ah receptor in marine animals: Phylogenetic distribution and relationship to cytochrome P4501A inducibility

    Mar. Environ. Res.

    (1992)
  • A.R. Hargens et al.

    High capillary permeability in fishes

    Comp. Biochem. Physiol.

    (1974)
  • T. Helder

    Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on early life stages of the pike (Esox lucius L.)

    Sci. Total Environ.

    (1980)
  • T. Helder

    Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on early life stages of rainbow trout (Salmo gairdneri Richardson)

    Toxicology

    (1981)
  • T.R. Henry et al.

    Early life stage toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in zebrafish (Danio rerio)

    Toxicol. Appl. Pharmacol.

    (1997)
  • J.H. Luft

    Capillary permeability. I. Structural consideration

  • D.J. Nichols

    Fluid volumes in rainbow trout, Salmo gairdneri: Application of compartmental analysis

    Comp. Biochem. Physiol.

    (1987)
  • J.R. Olson

    Metabolism and disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin in guinea pigs

    Toxicol. Appl. Pharmacol.

    (1986)
  • R. Wannemacher et al.

    Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on reproduction and oogenesis in zebrafish (Brachydanio rerio)

    Chemosphere

    (1992)
  • J.D. Wisk et al.

    Comparison of the toxicity of several polychlorinated dibenzo-p-dioxins and 2,3,7,8-tetrachlorodibenzofuran in embryos of the Japanese medaka (Oryzias latipes)

    Chemosphere

    (1990)
  • E.W. Zabel et al.

    Toxic equivalency factors of polychlorinated dibenzo-p-dioxin, dibenzofuran and biphenyl congeners based on early life stage mortality in rainbow trout (Oncorhynchus mykiss)

    Aquat. Toxicol.

    (1995)
  • W.S. Abbott

    A method of computing the effectiveness of an insecticide

    J. Econ. Entomol.

    (1925)
  • E.K. Balon

    Early ontogeny of the lake charr, Salvelinus (Christivomer) namaycush

  • K.M. Burbach et al.

    Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor

    Proc. Natl. Acad. Sci. USA

    (1992)
  • P.M. Cook et al.

    The TCDD toxicity equivalence approach for characterization of trout early life stage mortality risks associated with exposures to TCDD and related chemicals

  • DeWinden, P. J. J, van Donselaar, E. G, and, Herwig, H. J. 1994, Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on...
  • P.M. Fernandez-Salguero et al.

    Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor

    Science

    (1995)
  • J.M. Frasca et al.

    A routine technique for double staining ultrathin sections using uranyl and lead salts

    J. Cell Biol.

    (1965)
  • P.D. Guiney et al.

    Assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced sac fry mortality in lake trout (Salvelinus namaycush) from different regions of the Great Lakes

    Can. J. Fish. Aquat. Sci.

    (1996)
  • Hamilton, M. A., Russo, R. C., and Thurston, R. V.1977. Trimmed Spearman–Karber method for estimating median lethal...
  • M.A. Hayat

    Positive staining

  • Cited by (56)

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

      2021, Aquatic Toxicology
      Citation Excerpt :

      In zebrafish, TCDD exposure induces cyp1a mRNA in the endothelium as early as 24 hours post fertilization (hpf), preceding any signs of toxicity (Andreasen et al., 2002). Previous research also demonstrated that TCDD exposure produces a number of aberrant vascular phenotypes during development in multiple fish species, including: regression of the yolk vasculature (medaka; Cantrell et al., 1996), retrobulbar capillary hemorrhaging (lake trout; Guiney et al., 2000), decreased blood perfusion in the dorsal midbrain (Dong et al., 2002), inhibited growth and remodeling of the common cardinal vein (zebrafish; Bello et al., 2004), and malformation of the prosencephalic artery (zebrafish; Teraoka et al., 2010). Although the vasculature throughout the body is composed of endothelial cells, mural cells, and extracellular matrix, the vasculature is not homogenous (Aird, 2012); rather, it is specialized to the organs and tissues it innervates.

    • Heart development in two populations of Atlantic killifish (Fundulus heteroclitus) following exposure to a polycyclic aromatic hydrocarbon mixture

      2021, Ecotoxicology and Environmental Safety
      Citation Excerpt :

      In early life stages, disruption of blood flow is typically not lethal as diffusion serves to exchange gases, nutrients, and wastes (Burggren et al., 2004). However, once transition from diffusion to convective flow occurs after hatching, abnormalities within the circulatory system have more pronounced effects and often lead to mortality (Burggren et al., 2004; Guiney et al., 2000). In this study, the histochip proved valuable in that we were able to increase sample sizes, compare embryos on the same slide, and save cost and time.

    • Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells

      2019, Science of the Total Environment
      Citation Excerpt :

      Thus, whether prenatal TCDD exposure directly contributes to congenital heart diseases remains unknown. In animals, experiments showed that the developing heart is sensitive to dioxins and dioxin-like polychlorinated biphenyls (PCBs) (Kopf and Walker, 2009), as dioxin impairs cardiac development, morphology, and/or function in different species (Cantrell et al., 1996; Hornung et al., 1999; Guiney et al., 2000; Antkiewicz et al., 2005; Walker and Catron, 2000; Sommer et al., 2005; Thackaberry et al., 2005; Aragon et al., 2008; Carreira et al., 2015a). While this is consistent with findings in human populations, the underlying mechanism has not been fully delineated.

    • Environmental Pollutants on Angiogenesis and Vascular Development

      2018, Comprehensive Toxicology: Third Edition
    View all citing articles on Scopus
    View full text