UNDERSTANDING OVARIAN CONTROL IN RARE BIOMEDICAL MODELS

[unreadable] DESCRIPTION (provided by applicant): The candidate in this application will receive state-of-the art training while advancing scholarly knowledge on ovarian cycle control in felids (cats). Specific objectives are to investigate the mechanisms regulating ovarian activity, develop effective protocols for ovarian inhibition, and to apply these protocols to improve ovarian response to gonadotropin stimulation for AI and IVF. This, in turn, will help propagate cats valuable to biomedical research and conserve endangered felid species. Many rare cat populations are difficult to manage due to poor reproductive capacity, physical and behavioral obstacles to breeding success, and limitations on transporting animals between institutions. Unfortunately, females also experience low pregnancy success after Al and IVF due, in part, to high variability in ovarian response to exogenous gonadotropins. Controlling the ovary prior to ovulation induction improves pregnancy success in some species, but this concept has not been tested in an induced ovulator such as the cat. This project will combine basic and applied research to characterize the female response to four ovarian cycle inhibitors: 1) leuprolide acetate (Lupron), a gonadotropin releasing hormone (GnRH) agonist; 2) Antide, a GnRH antagonist; 3) levonorgestrel (Norplant), a progestogen implant; and 4) altrenogest (Regumate), an oral progestogen. The impact of ovarian cycle inhibition prior to gonadotropin stimulation will be examined at three sites: 1) the ovary during hormonal therapy, 2) the follicle and oocyte after gonadotropin stimulation, and 3) the uterus after ovulation induction and AI. Findings will be applied to rare felid models used in biomedical research and selected rare felid species to enhance propagation success. This research program is designed to provide a multidisciplinary, integrative training opportunity that will allow the candidate to advance as a reproductive physiologist with expertise in endocrinology, immunoassay development, noninvasive hormone monitoring, gamete metabolism, laparoscopy, AI, IVF, immunohistochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and histology. Research benefits include: 1) understanding mechanisms for controlling ovarian function in felids, 2) characterizing the impact of ovarian cycle inhibition prior to exogenous gonadotropin stimulation, 3) developing a research strategy for investigating complex mechanisms of female infertility, and 4) enhancing the efficiency of feline model propagation to ensure continued availability of cats for biomedical research and species conservation.