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Theriogenology2013; 80(9); 1006-1016; doi: 10.1016/j.theriogenology.2013.07.029

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

Abstract: 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.
Publication Date: 2013-08-30 PubMed ID: 23998737DOI: 10.1016/j.theriogenology.2013.07.029Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research study aimed to test the contraceptive effects of the compound RTI-4587-073(l) on male horses without influencing their sexual behavior. The results showed that a single dose of the compound led to a significant reduction in sperm count and motility, which was fully reversible after around 71 days, without changing the animal’s sexual behavior.

Research Objective

  • The primary goal of this research was to evaluate the effectiveness of the indenopyridine derivative RTI-4587-073(l) as a potential candidate for male contraception in horses.
  • To ensure the product would not negatively impact the horses’ life, the study aimed to assess whether this compound would affect the sexual behavior of the stallions.

Methodology

  • The researchers administered a single dose of the compound (12.5 mg/kg) orally to three miniature horse stallions (labelled as the “treated” group).
  • For comparison, three other miniature horse stallions were given a placebo (forming the “control” group).
  • The study collected and evaluated semen from all stallions twice weekly for three weeks before the treatment and 13 weeks following the treatment.
  • Sexual behavior was recorded and analyzed throughout this period.
  • Two sets of testicular dimensions were recorded: one before the treatment and the other during the post-treatment period.
  • Blood samples were also drawn for endocrine evaluation.

Results

  • The single administration of RTI-4587-073(l) caused severe oligoasthenozoospermia (low sperm count and low motility) in the treated stallions, which resulted in a large number of immature germ cells in their semen. This indicates that the compound was effective in inhibiting testicular functionality.
  • An increase in FSH (follicle-stimulating hormone) concentrations was also noted in the treated stallions, further signalling the impact of the compound on their reproductive system.
  • All these impacts were, however, found to be reversible within approximately 71 days.
  • The sexual behavior of the horses, including libido and copulatory behavior, remained unchanged by the treatment, validating the researchers’ hypothesis and essential criteria that the contraceptive should not affect the sexual behavior of the animals.

Conclusion

  • Given the results, the research concludes that RTI-4587-073(l) is a promising candidate for male contraception in domestic stallions.
  • In the light of these findings, the study suggests further research to test the potential of this compound for fertility control in wildlife and even humans.

Cite This Article

APA
Pozor MA, Macpherson ML, McDonnell SM, Nollin M, Roser JF, Love C, Runyon S, Thomas BF, Troedsson MH. (2013). Indenopyride derivative RTI-4587-073(l): a candidate for male contraception in stallions. Theriogenology, 80(9), 1006-1016. https://doi.org/10.1016/j.theriogenology.2013.07.029

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 80
Issue: 9
Pages: 1006-1016
PII: S0093-691X(13)00300-2

Researcher Affiliations

Pozor, Malgorzata A
  • Department of Large Animal Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA. Electronic address: PozorM@ufl.edu.
Macpherson, Margo L
    McDonnell, Sue M
      Nollin, Maggie
        Roser, Janet F
          Love, Charles
            Runyon, Scott
              Thomas, Brian F
                Troedsson, Mats H

                  MeSH Terms

                  • Animals
                  • Contraception / methods
                  • Contraception / veterinary
                  • Contraceptive Agents, Male / pharmacology
                  • Estradiol / blood
                  • Follicle Stimulating Hormone / blood
                  • Horses / physiology
                  • Indenes / pharmacology
                  • Inhibins / blood
                  • Luteinizing Hormone / blood
                  • Male
                  • Piperidines / pharmacology
                  • Semen Analysis
                  • Sexual Behavior, Animal / drug effects
                  • Testis / drug effects
                  • Testosterone / blood

                  Citations

                  This article has been cited 5 times.
                  1. Górecka-Bruzda A, Jaworska J, Stanley CR. The Social and Reproductive Challenges Faced by Free-Roaming Horse (Equus caballus) Stallions.. Animals (Basel) 2023 Mar 24;13(7).
                    doi: 10.3390/ani13071151pubmed: 37048406google scholar: lookup
                  2. Service CA, Puri D, Hsieh TC, Patel DP. Emerging concepts in male contraception: a narrative review of novel, hormonal and non-hormonal options.. Ther Adv Reprod Health 2023 Jan-Dec;17:26334941221138323.
                    doi: 10.1177/26334941221138323pubmed: 36909934google scholar: lookup
                  3. Long JE, Lee MS, Blithe DL. Update on Novel Hormonal and Nonhormonal Male Contraceptive Development.. J Clin Endocrinol Metab 2021 May 13;106(6):e2381-e2392.
                    doi: 10.1210/clinem/dgab034pubmed: 33481994google scholar: lookup
                  4. Thirumalai A, Page ST. Recent Developments in Male Contraception.. Drugs 2019 Jan;79(1):11-20.
                    doi: 10.1007/s40265-018-1038-8pubmed: 30588563google scholar: lookup
                  5. Blithe DL. Pipeline for contraceptive development.. Fertil Steril 2016 Nov;106(6):1295-1302.