Hofsteen, P., Mehta, V., Kim, M.S., Peterson, R.E., and Heideman, W. (2013) TCDD Inhibits Heart Regeneration in Adult Zebrafish. Toxicological sciences : an official journal of the Society of Toxicology. 132(1):211-221.
Normal adult zebrafish can completely regenerate lost myocardium following partial amputation of the ventricle apex. We report
that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly impairs this regeneration. Adult male zebrafish were injected with vehicle (control) or TCDD
(70 ng/g, ip) one day prior to partial amputation of the ventricle apex. Gross observation and histological analysis of the
amputated heart at 21 days post amputation (dpa) revealed that TCDD-exposed fish had not progressed beyond the initial clot
formation stage, while the vehicle control fish showed substantial recovery and almost complete resolution of the formed clot.
In contrast, hearts that were not surgically wounded showed no signs of TCDD-toxicity. Striking features in the TCDD-exposed
hearts were the absence of the normal sheath of new tissue enveloping the wound, and the absence of intense cell proliferation
at the site of the wound. In addition, the patterns of collagen deposition at the wound site were different between the TCDD
and vehicle groups. Because the receptor for TCDD is the AHR ligand-activated transcriptional regulator, we examined the
effects of TCDD exposure on gene expression in the ventricle using DNA microarrays. Samples were collected just prior to
amputation and at 6 h and 7 d post amputation. TCDD-pretreated hearts had dysregulated expression of genes involved in heart
function, tissue regeneration, cell growth, and extracellular matrix. Because embryonic, but not adult, hearts are major
targets for TCDD-induced cardiotoxicity, we speculate that the need for embryonic-like cells in regeneration is connected
with the effects of TCDD in inhibiting the response to wounding.
No data available
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