Michelle Kossack, Postdoctoral Research Associate, Pathology and Laboratory Medicine
Abstract Title: Sex and heart health: differential effects of juvenile 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on cardiovascular function in female zebrafish.
Abstract: Exposure to environmental contamination is a significant factor in the global rise of infertility rates and is an important modifier of cardiac development and health. Approximately 20-30% of congenital heart disease is thought to be caused by exposure to environmental pollutants. Many contaminants affect multiple organs in the body, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent dioxin congener and aryl hydrocarbon receptor (AHR) agonist, which is classified as a reproductive toxicant and causes lethal cardiac phenotypes in embryonic zebrafish. However, the mechanism by which developmental exposure to dioxins may contribute to adult cardiac dysfunction is unknown. Furthermore, it is not known whether TCDD induced damage to the ovary, exacerbates TCDD-induced cardiac injuries. To address these important questions, we are using the zebrafish model. Zebrafish are a powerful model for studying cardiovascular and ovarian health as many of the critical genes that orchestrate heart and ovary development are evolutionarily conserved between humans and fish. Here, we show that juvenile exposure to sub-lethal levels of TCDD (50 parts-per-trillion) at 20 and 50 days post fertilization results in long-term cardiac dysfunction. We monitored the cardiac health of exposed and control fish using electrocardiograms and echocardiograms and found that electrical conduction in the heart was significantly altered by TCDD exposure, with females being more significantly impacted than males. While echocardiograms showed that TCDD-exposed individuals are able to functionally compensate over time and maintain normal blood flow, preliminary histological analysis suggests that juvenile TCDD exposure induces epicardial pathology in females. The epicardium, the outermost layer of the heart, has critical roles in cardiac development, disease progression, and repair. Previous work demonstrates that the progenitor cells which give rise to the epicardium, as well as the epicardium itself, are cellular targets of TCDD. Our observations indicate that the epicardium continues to be sensitive to TCDD exposure and also suggest a critical and uninvestigated interaction between sex and cardiovascular health in the response to environmental containment exposure.