Identifying critical mediators of ovarian and cardiovascular health - PROJECT SUMMARY/ABSTRACT Environmental contaminant exposure accounts for 20-30% of the known congenital heart disease and is a significant driver of adult heart disease. Likewise, exposure to environmental contamination also adversely affects ovarian health and is thought to be a significant factor in the global rise of infertility rates. Cardiac health is impacted by ovarian health and vice versa. While the heart supplies the ovary with necessary oxygen, the ovary produces estrogen, which is cardioprotective. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure is associated with both cardiac and ovarian dysfunction. However, the effects of TCDD exposure on organ health are often studied in isolation and, therefore, the interaction between the two systems is lost. This proposal investigates the central hypothesis that juvenile TCDD exposure affects female heart health by compromising ovarian function. There is a critical need to understand the mediators of TCDD toxicity in both the heart and ovary to provide effective treatment for heart disease and infertility. In Aim 1, I will determine the ovarian contribution to TCDD-induced cardiovascular toxicity. In Aim 2, I will use single-cell sequencing to identify unique and shared cellular and molecular targets of TCDD in the heart and ovary. In Aim 3, I will determine whether TCDD-induced infertility results from disrupted functioning of the blood-follicle barrier. My long-term goal is to become an independent investigator at an R1 institution studying reproductive toxicology. My lab will use zebrafish to model human reproductive development and exposure to environmental chemicals. I have designed a training plan that will expand my scientific skill set as well as guide my professional development. My mentor, Dr. Jessica Plavicki, and co-mentor, Dr. Jodi Flaws, will facilitate my growth and provide research and career support. I have assembled an advisory team that is made up of experts who will provide critical research and career guidance. By achieving the specific milestones outlined in my training plan and research strategy, I will develop a strong foundation for my future research program and academic career.
