Multifactorial regulation of ovarian function in fish

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The long term goal of my research program is to understand the hormonal regulation of ovarian development in fish, focusing on the acquisition of follicular cell maturational and ovulatory competency. Using zebrafish as our model species, our research addresses fundamental questions regarding which hormones affect follicular development and if there are hallmark responses that determine whether a follicle is destined to mature and ovulate. This research is important not only to understanding the reproductive biology of fish, but also to understanding and monitoring the toxicological effects of endocrine disrupting compounds and other environmental factors in our waterways. The ovulation of a mature oocyte requires a series of coordinated events that lead to follicular somatic cell differentiation and oocyte development. The final stages of follicular recruitment leading to ovulation are dependant on luteinizing hormone (LH), sex steroids and prostaglandins (PG). The absence of these hormones leads to anovulation and follicle degeneration. However, the precise features that contribute to successful follicle development remains elusive, and are further complicated by the fact that many locally derived hormones, growth factors and other regulators are critical to these processes. Over the next 5 years we will advance our understanding the hormonal regulation of ovarian development in zebrafish by focusing on the acquisition of follicular cell maturational and ovulatory competency. First, we will investigate the timing, regulation and dependence of LH, the fish-specific progesterone derivative 17a,20ßP and its nuclear receptor, and PG in controlling the expression and activities of proteases which are required for ovulation. Second, we will investigate microRNAs (miRNAs) that are suspected of influencing the development of the ovarian follicle during the periovulatory period. These studies will include measuring the expression of selected miRNA in relation to spontaneous and hormonally induced ovulation. We will also modulate miRNA levels and determine how this affects steroid and PG biosynthesis and the induction of oocyte maturation. Lastly, we will investigate the insulin-like growth factor (IGF) family, which consists of multiple ligands, receptors and binding proteins, on the physiology of the ovarian follicle. Specifically, we will determine how the IGF3 ligand and IGF receptor antagonists affect the production of hormones (steroids and PGs) and expression of selected target genes. Collectively, these studies will address important and novel questions concerning the hormonal control of oocyte maturation and ovulation in the zebrafish that are relevant to both reproductive physiology and environmental toxicology. The planned studies will support my lab's ongoing global leadership in the areas of comparative endocrinology and environmental sciences, and provide a rich training environment for graduate and undergraduate trainees.