Journal
TOXICOLOGICAL SCIENCES
Volume 127, Issue 2, Pages 360-370Publisher
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfs103
Keywords
dioxin; developmental toxicity; AHR; zebrafish; cardiotoxicity
Categories
Funding
- National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) [R01 ES012716, T32 ES07015]
- University of Wisconsin Sea Grant Institute
- National Oceanic and Atmospheric Administration
- U.S. Department of Commerce [NA 16RG2257]
- Sea Grant Project [R/BT-20, R/BT-22]
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The embryos of teleost fish are exquisitely sensitive to the toxic effects of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, several lines of evidence suggest that adults are less sensitive to TCDD. To better understand and characterize this difference between early life stage and adults, we exposed zebrafish (Danio rerio) to graded TCDD concentrations at different ages. The LD50 for embryos exposed at 1 day post-fertilization (dpf) was more than an order of magnitude lower than it was for juveniles exposed at 30 dpf. The latency between exposure and response also increased with age. Embryo toxicity was characterized by marked cardiovascular collapse and heart malformation, whereas juveniles exposed at 30 dpf had no detectable cardiovascular toxicity. In juveniles, the effects of TCDD exposure included stunted growth, altered pigmentation, and skeletal malformations. Furthermore, the transcriptional profile produced in hearts exposed to TCDD as embryos had very little overlap with the transcriptional changes induced by TCDD at 30 dpf. The early cardiotoxic response was associated with fish exposed prior to metamorphosis from the larval to the adult body plan at approximately 14 dpf. Our results show conclusively that the developmental stage at the time of exposure controls the toxic response to TCDD.
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