The cardiovascular system is one of the most characteristic and important targets for developmental toxicity by
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD) in fish larvae. However, knowledge of the mechanism of
TCDD-induced
edema after heterodimerization of
aryl hydrocarbon receptor type 2 (AHR2) and
AHR nuclear translocator type 1 (ARNT1) is still limited. In the present study, microscopic analysis with a high-speed camera revealed that
TCDD increased the size of a small cavity between the heart and body wall in early eleutheroembryos, a toxic effect that we designate as precardiac
edema. A concentration-response curve for precardiac
edema at 2 days post fertilization (dpf) showed close similarity to that for conventional pericardial
edema at 3 dpf. Precardiac
edema caused by
TCDD was reduced by
morpholino knockdown of AHR2 and ARNT1, as well as by an
antioxidant (
ascorbic acid). A selective inhibitor of
cyclooxygenase type 2 (COX2),
NS398, also markedly inhibited
TCDD-induced precardiac
edema. A
thromboxane receptor (TP) antagonist, ICI-192,605 almost abolished
TCDD-induced precardiac
edema and this effect was canceled by
U46619, a TP agonist, which was not influential in the action of
TCDD by itself. Knockdown of COX2b and
thromboxane A synthase 1 (TBXS), but not COX2a, strongly reduced
TCDD-induced precardiac
edema. Knockdown of COX2b was without effect on mesencephalic circulation failure caused by
TCDD. The
edema by
TCDD was also inhibited by knockdown of c-mpl, a
thrombopoietin receptor necessary for thromobocyte production. Finally, induction of COX2b, but not COX2a, by
TCDD was seen in eleutheroembryos at 3 dpf. These results suggest a role of the COX2b-thromboxane pathway in precardiac
edema formation following
TCDD exposure in developing zebrafish.