Acute and Chronic Effects of a Contraceptive Compound RTI‐4587‐073(l) on Testicular Histology and Endocrine Function in Miniature Horse Stallions

Abstract

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.

Ultrasonographic and morphological sequelae to repeated testicular biopsies in stallions in relation to the lateral branching of the testicular artery

“…As previously reported, there was no significant change in testicular volume in treated or control stallions (Pozor et al . ). Three testes from 2 control stallions ( Testes 4–6 ) had similar or slightly higher volumes following all biopsy procedures than during the baseline period, while the other 3 testes ( Testes 1–3 ) from the control stallions were slightly smaller than before ( Supplementary Item 1 ).…”

“…The changes in the semen parameters were previously reported (Pozor et al . ). There were no changes in the analysed semen parameters in the 3 stallions from the control group (Pozor et al .…”

“…There were no changes in the analysed semen parameters in the 3 stallions from the control group (Pozor et al . ).…”

“…One treated stallion had a dramatic bilateral change in testicular volume, which was attributed to the antispermatogenic compound (Pozor et al . ); however, the effect of the biopsy procedures on these testes cannot be excluded.…”

“…Testicular dimensions were determined, and testicular volumes were calculated as described previously (Pozor et al . ).…”