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ToxSci Advance Access originally published online on January 12, 2004
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Toxicological Sciences 78, 78-87 (2004)
Copyright © 2004 by the Society of Toxicology


REGULAR ARTICLE

Water Permeability and TCDD-Induced Edema in Zebrafish Early-Life Stages

Adrian J. Hill*,2, Susan M. Bello*,2, Amy L. Prasch{dagger}, Richard E. Peterson* and Warren Heideman*,1

* School of Pharmacy and the {dagger} Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53705

1 To whom correspondence should be addressed at the School of Pharmacy, University of Wisconsin, 777 Highland Ave., Madison, WI 53705-2222. Fax: (608) 265-3316. E-mail: wheidema{at}wisc.edu.

ABSTRACT

A common response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in teleost embryos is blue-sac disease, characterized by pericardial and yolk-sac edema. The cellular and extracellular fluids of freshwater fish are hyperosmotic compared to the surrounding water. In order to be in osmotic balance, freshwater fish must maintain a barrier to minimize water entry and excrete excess water that passes the barrier. We hypothesized that edema observed in TCDD-exposed zebrafish was caused by a failure of a barrier to incoming water. As a test of this hypothesis, we removed the osmotic gradient that drives water entry by increasing the osmolarity of the surrounding water with mannitol. Abolishing the osmotic gradient between the interior body fluids and the water environment of the developing zebrafish significantly reduced both pericardial and yolk-sac edema. When added after edema formation had already started, mannitol only partially reversed pre-existing edema. An alternate hypothesis is that TCDD impairs water excretion, allowing water to accumulate as edema fluid. However, we were unable to demonstrate an alteration in kidney function: expression of early markers for kidney development appeared normal, and we did not observe TCDD-induced changes in kidney filtration. An alteration in the overall shape of the kidney was observed, but this may be a consequence of compression by edema. In conclusion, TCDD exposure may inhibit the function of a permeability barrier to water, which is critical for maintaining osmotic balance in early development.

Key Words: AHR2; ARNT2; TCDD; zebrafish; blue-sac syndrome; edema.


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