Acute and chronic effects of a contraceptive compound RTI-4587-073(l) on testicular histology and endocrine function in miniature horse stallions

Reprod Domest Anim. 2014 Jun;49(3):392-402. doi: 10.1111/rda.12286. Epub 2014 Mar 5.


The objective of this study was to evaluate acute endocrine effects as well as histological changes in testicular parenchyma induced by the contraceptive compound RTI-4587-073(l). Six miniature stallions were used in this experiment. The treatment group (n = 3) received one oral dose of 12.5 mg/kg of RTI-4587-073(l), and the control group (n = 3) received placebo only. The stallions' baseline parameters (semen, testicular dimensions, endocrine values) were collected and recorded for 5 weeks before treatment and for 6 weeks after treatment. Multiple blood samples were collected for endocrine analysis. Testicular biopsies were obtained before treatment, 1 day after treatment and every other week after treatment. Ultrasound exams were performed to monitor the dimensions of the stallions' testes. All stallions were castrated 6 weeks after treatment. Sperm numbers, motility and percentage of morphologically normal sperm decreased (p < 0.05), while the number of immature germ cells increased in ejaculates from treated animals (p < 0.05). Serum concentrations of inhibin and follicle-stimulating hormone did not change. Testosterone concentrations initially transiently decreased (p < 0.05) after administration of RTI-4587-073(l), and increased several days later (p < 0.05). Testicular content of testosterone and estradiol 17-β was lower in treated stallions than in control stallions on Day 1 after treatment (p < 0.05). Severe disorganization of the seminiferous tubules, significant loss of immature germ cells and complete depletion of elongated spermatids were observed in testicular biopsies obtained from treated stallions 1 day, 2 and 4 weeks after treatment. These changes were still present in the testicular samples taken from treated stallions after castration. The results of this study confirmed that RTI-4587-073(l) has antispermatogenic effects in stallions. Furthermore, we concluded that this compound causes acute sloughing of immature germ cells from the seminiferous tubules. RTI-4587-073(l) has significant but transient effects on Leydig cell function in stallions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contraceptive Agents, Male / pharmacology*
  • Estradiol / analysis*
  • Follicle Stimulating Hormone / blood
  • Horses*
  • Indenes / pharmacology*
  • Inhibins / analysis
  • Inhibins / blood
  • Luteinizing Hormone / blood
  • Male
  • Piperidines / pharmacology*
  • Seminiferous Epithelium / cytology
  • Seminiferous Epithelium / drug effects
  • Sperm Count
  • Sperm Motility / drug effects
  • Spermatocidal Agents / pharmacology
  • Spermatozoa / drug effects
  • Testis / anatomy & histology
  • Testis / drug effects*
  • Testis / physiology
  • Testosterone / analysis*
  • Testosterone / blood


  • CDB 4022
  • Contraceptive Agents, Male
  • Indenes
  • Piperidines
  • Spermatocidal Agents
  • Testosterone
  • Estradiol
  • Inhibins
  • Luteinizing Hormone
  • Follicle Stimulating Hormone