1. Sponsor Organization: NIH/NIEHS

2. Project Title: 05673-03 MECHANISM OF TCDD-INDUCED EFFECTS ON CHICK CARDIOGENESIS

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

The long term goal of this research is to decrease the uncertainty of the risk that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poses to human fetal development by improving our understanding of the mechanism of developmental toxicity produced by TCDD. In laboratory animals and humans exposed to TCDD or to TCDD-like chemicals, developmental abnormalities appear to arise from a disruption of growth and differentiation of epithelial and/or ectodermal tissues. In the chick embryo, TCDD appears to disrupt growth and differentiation of heart endothelial cells giving rise to cardiac septal defects. Using septal morphogenesis as a model I plan to (1) investigate whether TCDD exposure disrupts epithelial to mesehymal transformation of cardiac endothelial cells, (2) identify specific cell types and/or target genes affect by TCDD in this process using in situ hybridization and immunohistochemistry, and (3) determine whether the effects of TCDD are mediated via the aryl hydrocarbon receptor (AhR) by (a) determining the tissue-specific expression of the AhR and (b) studying the structure activity relationship for induction of cardiac malformations by other AhR agonists. Ultimately, this research will provide insight into the tissues and organs at highest risk to the impact of TCDD during in utero exposure of the human fetus.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Avian
• Study Type:
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Reproductive
• Hormonal Measures:
  • Ah Receptor
• Level Of Study:
• Chemistry Metabolism:
• Life Stage:
  • Embryo
  • Growth
• Risk Assessment:

10. Chemical Agents:

• Dioxins

11. Performing Institution:

• UNIVERSITY OF WISCONSIN MADISON

12. Contact:

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