title: 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.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Pozor
authors.forename: G
authors.initials: G
authors.lastname: Zambrano
authors.forename: J
authors.initials: J
authors.lastname: Roser
authors.forename: R
authors.initials: R
authors.lastname: Hess
authors.forename: S
authors.initials: S
authors.lastname: Runyon
authors.forename: E
authors.initials: E
authors.lastname: Runcan
authors.forename: B F
authors.initials: BF
authors.lastname: Thomas
authors.forename: D
authors.initials: D
authors.lastname: Dymock
authors.forename: M L
authors.initials: ML
authors.lastname: Macpherson
authors.forename: M H
authors.initials: MH
authors.lastname: Troedsson
authors.forename: A
authors.initials: A
authors.lastname: Kelleman
mesh_terms: D000818:Animals; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D004958:Estradiol / Q000032:analysis*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006736:Horses; D007192:Indenes / Q000494:pharmacology*; D007265:Inhibins / Q000032:analysis / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D012670:Seminiferous Epithelium / Q000166:cytology / Q000187:drug effects; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013089:Spermatocidal Agents / Q000494:pharmacology; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000032:analysis* / Q000097:blood
chemical_list: C435918:CDB 4022; D003272:Contraceptive Agents, Male; D007192:Indenes; D010880:Piperidines; D013089:Spermatocidal Agents; D013739:Testosterone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone