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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01RR017310-04
Application #
6912666
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Watson, William T
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
4
Fiscal Year
2005
Total Cost
$114,848
Indirect Cost
Name
Smithsonian Institution
Department
Type
DUNS #
089522580
City
Arlington
State
VA
Country
United States
Zip Code
22202
Stewart, Rosemary A; Crosier, Adrienne E; Pelican, Katharine M et al. (2015) Progestin priming before gonadotrophin stimulation and AI improves embryo development and normalises luteal function in the cat. Reprod Fertil Dev 27:360-71
Stewart, Rosemary A; Pelican, Katharine M; Crosier, Adrienne E et al. (2012) Oral progestin priming increases ovarian sensitivity to gonadotropin stimulation and improves luteal function in the cat. Biol Reprod 87:137
Stewart, R A; Pelican, K M; Brown, J L et al. (2010) Oral progestin induces rapid, reversible suppression of ovarian activity in the cat. Gen Comp Endocrinol 166:409-16
Pelican, Katharine M; Spindler, Rebecca E; Pukazhenthi, Budhan S et al. (2010) Progestin exposure before gonadotropin stimulation improves embryo development after in vitro fertilization in the domestic cat. Biol Reprod 83:558-67
Pelican, Katharine M; Wildt, David E; Ottinger, Mary A et al. (2008) Priming with progestin, but not GnRH antagonist, induces a consistent endocrine response to exogenous gonadotropins in induced and spontaneously ovulating cats. Domest Anim Endocrinol 34:160-75
Pelican, Katharine M; Wildt, David E; Pukazhenthi, Budhan et al. (2006) Ovarian control for assisted reproduction in the domestic cat and wild felids. Theriogenology 66:37-48
Pelican, K M; Brown, J L; Wildt, D E et al. (2005) Short term suppression of follicular recruitment and spontaneous ovulation in the cat using levonorgestrel versus a GnRH antagonist. Gen Comp Endocrinol 144:110-21