Up to 40% of female infertility can be attributed to ovary dysfunction. There are many known markers of ovary dysfunction, yet the underlying cellular mechanisms that disrupt normal function often remain elusive. Our ability to understand the etiology of ovarian dysfunction and to develop effective treatments is hindered by our limited knowledge of vascular contributions to ovarian health. The observed rise in female infertility over the past 50 years highlights our need to understand the connection between ovarian dysfunction and environmental toxicant exposure. Dioxins are persistent, global environmental toxicants of concern formed through industrial processes such as the burning of petroleum-based products. Exposure to dioxin has been associated with increased time to pregnancy and reduced reproductive outcomes in women. However, it is not known how developmental exposure to dioxin effects the formation of the reproductive organs, nor how exposure contributes to ovary dysfunction. Zebrafish embryonic development is rapid and occurs ex vivo. Zebrafish embryos exposed to TCDD, a potent dioxin congener, have vascular malformations in the brain, heart, and periphery. Furthermore, juvenile exposure to dioxin causes reduced fertility in the adult female zebrafish. Vascularization is an essential part of female fertility. Very little is known about how vascularization contributes to ovary development and subsequent fertility. Additionally, it is not known how developmental TCDD exposure affects the formation of the ovarian vasculature. The proposed study will generate a timeline of vascular development in the zebrafish ovary and determine the windows of susceptibility to dioxin-induced vascular dysfunction (Aim1). Furthermore, this study will be the first to determine the physiological underpinnings of TCDD-induced infertility by identifying the cellular and molecular targets of TCDD in pericytes (Aim 2). Investigating the vascular contribution to infertility will significantly enhance our understanding and treatment of reproductive disorders and infertility in humans. This proposal will take advantage of my experience in zebrafish reproductive development, while affording me the opportunity to develop a new technical skillset and deep understanding of toxicology. I have developed a comprehensive, yet achievable, training plan focused on developing the skills needed to achieve my long-term goal of becoming an independent investigator. This plan will enhance my technical skills, writing, grantsmanship, teaching, and mentoring with feedback from my training committee: Dr. Jessica Plavicki (sponsor), Dr. Mark Hahn (co- sponsor), Dr. Kim Boekelheide (collaborator), and Dr. Richard Freiman (collaborator). My training committee has extensive experience in reproductive and developmental toxicology as well as training postdocs for successful careers in academia.