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

The research article presents the investigation of the effects of contraceptive compound named RTI-4587-073(l) on endocrine function and testicular morphology in miniature horse stallions. The study finds that this compound has a negative impact on sperm production and causes significant but temporary changes in Leydig cell function, which are cells in the testes responsible for producing testosterone.

Study Design and Procedures

• The study involved six miniature horse stallions, divided into a treatment group and a control group, with three stallions each.
• The treatment group received a dose of 12.5 mg/kg of a contraceptive compound called RTI-4587-073(l), while the control group was given a placebo.
• Prior to treatment and 6 weeks post-treatment, various parameters such as semen samples, endocrine levels and testicular dimensions were collected and assessed.
• Testicular biopsies were taken before the treatment, a day after, and then bi-weekly post-treatment. Ultrasound exams were carried out to observe the stallions’ testes’ dimensions.

Results & Findings

• The sperm count, motility, and the percentage of normally formed sperm significantly decreased in the treated stallions.
• However, the number of immature germ cells in the ejaculates of treated horses showed an increase.
• Although the serum levels of inhibin and follicle-stimulating hormone remained the same, there was a short-lived drop in the testosterone levels after administering the contraceptive, which later surged a few days later.
• On the day following the treatment, testosterone and estradiol 17-β content in testes was markedly less in the treatment group compared to the control group.
• Stallions in the treatment group showed severe disorganization in the seminiferous tubules, a significant loss of immature germ cells and a total elimination of elongated spermatids, based on the biopsies obtained 1 day, 2 weeks, and 4 weeks post treatment.
• These alterations in the seminiferous tubules remained persistent in the samples acquired from the stallions after they had been castrated 6 weeks post-treatment.

Conclusions

• The study confirmed the contraceptive compound RTI-4587-073(l) possesses antispermatogenic effects in stallions, meaning it impedes the formation and maturity of sperms.
• Critically, it concluded that RTI-4587-073(l) also initiates acute sloughing of immature germ cells from the seminiferous tubules; essentially shedding off immature germ cells quite rapidly from their place of origin.
• Finally, RTI-4587-073(l) was found to have discernible but transient effects on Leydig cell function in stallions. Leydig cells in stallions are responsible for testosterone production.