Multifactorial Regulation of Ovarian Function in Fish

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The long-term objective of my research is to understand the mechanisms by which pituitary gonadotropins and ovarian derived sex steroids, eicosanoids and protein growth factors regulate ovarian development in fish. My research has contributed to defining the hormones and signal transduction pathways that mediate ovarian follicle cell survival, steroidogenesis, oocyte final maturation and ovulation and integrating these responses at the whole animal level in terms of effects on spawning success. Although there have been considerable advances in the study of events controlling preovulatory ovarian development, there continues to be significant gaps in our understanding of how a follicle is selected to mature and ovulate. My research over the next 5 years will investigate the hormonal regulation of ovarian development focusing on the acquisition of follicular cell maturational and ovulatory competency using the zebrafish as the model. The research will focus on two main topics. The first of these will characterize the ontogeny of eicosanoid synthesis and action during the preovulatory period focusing on the changes that occur as the follicle progresses through the mid-vitellogenic to the full grown stage of follicular development. These studies will investigate the expression and regulation of prostaglandin and leukotriene receptors in the ovarian follicle. Subsequent studies will investigate the downstream targets of eicosanoid action and identify proteases that contribute to ovarian follicle cell rupture and ovulation of the oocyte. Based on increasing evidence that ovarian derived growth factors play an integral role in ovarian development, my second major research focus will on the insulin-like growth factor and corticotropin releasing factor families, which include ligands, receptors and binding proteins. This research involves characterizing the expression and localization of these hormone family members during the preovulatory period and also their role in ovarian development through studies involving hormone/receptor antagonists or mRNA knockdown in order to examine the effects of loss of function on biological response. The knowledge gained by this research is fundamental to understanding reproductive fitness and provides the toolbox that enables examination of the mechanisms by which endocrine disrupting compounds and other environmental factors affect ovarian physiology in fish. The planned studies are designed to position my group as a global leader in the areas of comparative endocrinology and environmental sciences.