Disruption of erythropoiesis by dioxin in the zebrafish.
2,3,7,8-Tetrachlorodibenzo-p- dioxin (TCDD, or dioxin) causes early life stage mortality in a variety of fish species. We have used the zebrafish (Danio rerio) to study the cardiovascular effects of TCDD treatment over the time course of zebrafish development. Early TCDD exposure (6 ng/ml) starting at 4 hr postfertilization (hpf) produced reductions in blood flow and in the number of circulating erythrocytes. These defects were consistently observable by 72 hpf. However, these responses were not observed when TCDD exposure was delayed until 96 hpf or later. These results suggest a model in which TCDD interferes with cardiovascular and erythropoietic developmental processes that are normally completed by 96 hpf. This model is strengthened by the finding that TCDD exposure blocks the step in hematopoiesis in which developing zebrafish switch from the primitive phase to the definitive phase of erythropoiesis. We observed no effect of TCDD on the levels of circulating primitive erythrocytes before 72 hpf and the expression of markers for early hematopoiesis, GATA-1 and GATA-2. However, early TCDD exposure prevented the appearance of definitive phase erythrocytes. TCDD produced a small delay in the migration of blood cells expressing SCL from the intermediate cell mass to the dorsal mesentery and dorsal aorta. Despite the decrease in blood flow produced by TCDD, confocal microscopy of the trunk vasculature by using a Tie2/green fluorescence protein endothelial marker at 48, 60, 72, and 96 hpf of TCDD-exposed (4 hpf) revealed no apparent defects in blood vessel structure.
Belair
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NIEHS Developmental and Molecular Toxicology Center and School of Pharmacy, University of Wisconsin, Madison 53705, USA.
Peterson
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Heideman
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D000740:Anemia / Q000139:chemically induced; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001808:Blood Vessels / Q000196:embryology; D002319:Cardiovascular System / Q000196:embryology; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology; D004785:Environmental Pollutants / Q000506:poisoning*; D004920:Erythropoiesis / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006410:Hematopoiesis / Q000235:genetics; D000072317:Polychlorinated Dibenzodioxins / Q000506:poisoning*; D015027:Zebrafish / Q000196:embryology*
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins