Dioxin inhibits zebrafish epicardium and proepicardium development

Area of Science:

• Developmental biology
• Toxicology
• Cardiovascular research

Background:

• Environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to disrupt cardiac development.
• The period of zebrafish embryonic development when the heart is most sensitive to TCDD coincides with epicardium formation.

Purpose of the Study:

• To investigate if TCDD exposure inhibits epicardium and proepicardium (PE) development in zebrafish.
• To determine the mechanism behind TCDD-induced cardiotoxicity during a critical developmental window.

Main Methods:

• Histology and fluorescence immunocytochemistry to examine epicardium formation in TCDD-exposed zebrafish.
• Live imaging and in situ hybridization to assess PE cluster formation and tcf21 gene expression.
• Assessing the impact of TCDD exposure at different stages of epicardial development.

Main Results:

• TCDD exposure prevented the formation of the epicardium and the proepicardium (PE) cluster.
• TCDD blocked the expression of the PE marker tcf21.
• TCDD inhibited the expansion of the epicardial layer across the heart, but did not affect existing epicardial cells.

Conclusions:

• TCDD-induced cardiotoxicity in zebrafish is likely due to the disruption of epicardial development.
• Inhibition of epicardium formation accounts for the temporal sensitivity to TCDD cardiotoxicity.
• Epicardium development is critical for normal heart development, and its disruption by TCDD has significant consequences.