During a 3 year period, simple protocols using administration of a highly potent gonadotropin releasing hormone (GnRH) agonist will be developed for planned, rapid, predictable, timed induction of estrus and fertile ovulation and pregnancy in research dogs. The methodology will be developed, refined and evaluated as to the scope of its applicability including use in bitches shortly after pregnancy failure, shortly after lactation, and after hormonal delay of ovulation , and as a tool for use in canine embryo transfer. Currently available methods for canine ovulation induction have negligible utility, in contrast to success obtained in other research animal species. The availability of the methodology to be developed will provide for more efficient and economical production of dogs for research and teaching use, for study and preservation of numerous canine models of human disease, and for responsible research evaluating the effect of reproductive state and pregnancy on physiological mechanisms most readily studied in dogs. The latter have not been feasible to date because dogs only ovulate 1 or 2 times a year and studies require large numbers of dogs or long times for completion. The method will involve GnRH agonist administration via subcutaneous osmotic minipumps with or without supplemental injections of the agonist to enhance follicle growth or trigger ovulation. Studies on LH and FSH released by various agonist doses will be done in intact dogs after more efficiently testing in an ovariectomized-bitch model system. An 80% or better success rate is expected based on a 50% success rate in preliminary studies. All critical studies will use confirmed early-anestrus beagle bitches and proper controls to preclude any concern about the significance of results. The best method will be tested for applicability in nonpregnant metestrus after prostaglandin induced luteolysis, post-weaning using dopamine agonist induced hypoprolacinemia, and after ovulation delay using progestin implants, as well as in mixed-breed dogs. Routine methods for monitoring efficacy will include quantitation of genital and vaginal changes, sex behavior, and serum levels of LH, FSH, estradiol and progesterone measured by radioimmunoassay for frequently collected serial blood samples.
