Indenopyride derivative RTI-4587-073(l): A candidate for male contraception in stallions

• Published in: Theriogenology 2013-12, Vol.80 (9), p.1006-1016
• Main Authors: Pozor, Malgorzata A., Macpherson, Margo L., McDonnell, Sue M., Nollin, Maggie, Roser, Janet F., Love, Charles, Runyon, Scott, Thomas, Brian F., Troedsson, Mats H.
• Format: Article
• Language: English
• Subjects: Animals; blood; contraception; Contraception - methods; Contraception - veterinary; Contraceptive Agents, Male - pharmacology; Estradiol - blood; Follicle Stimulating Hormone - blood; follicle-stimulating hormone; FSH; Horses - physiology; humans; Indenes - pharmacology; Indenopyridine; Inhibins - blood; libido; Luteinizing Hormone - blood; Male; Male contraception; Piperidines - pharmacology; semen; Semen Analysis; Sexual behavior; Sexual Behavior, Animal - drug effects; spermatozoa; Stallion semen; stallions; Testis - drug effects; Testosterone - blood; ultrasonography; Wildlife; wildlife damage management
• ISSN: 0093-691X; 1879-3231
• DOI: 10.1016/j.theriogenology.2013.07.029

The objective of this study was to determine whether an indenopyridine derivative RTI-4587-073(l) was a good candidate for male contraception in horses. We hypothesized that a single administration of RTI-4587-073(l) causes significant suppression of testicular function in stallions without affecting sexual behavior. Three Miniature horse stallions received a single dose of 12.5 mg/kg RTI-4587-073(l) orally (group “treated”), whereas three other Miniature horse stallions received placebo only (group “control”). Semen was collected and evaluated from all stallions twice a week for three baseline weeks and 13 post-treatment weeks. Sexual behavior was video-recorded and analyzed. Testicular dimensions were measured using ultrasonography, and blood samples were drawn for endocrine evaluation once before treatment and once a week during the post-treatment period. Single administration of RTI-4587-073(l) caused severe oligoasthenozoospermia (low sperm number and low motility), shedding large numbers of immature germ cells in semen, and increased FSH concentrations in treated stallions. These effects were fully reversible within ∼71 days. However, libido and copulatory behavior remained unchanged throughout the entire experiment. We concluded that RTI-4587-073(l) was a promising candidate for male contraceptive in domestic stallions. Further research should be performed to test this compound for fertility control in wildlife and humans.