Effect of Prograf (FK506) on spermatogenesis in rats.
Prograf (FK506) was given to male mature rats in a daily subcutaneous dose of 1 or 3 mg/kg/day for 2 weeks to investigate its effect on spermatogenesis. Prograf dose-dependently sperm counts and motility, but did not affect testosterone level in the serum of rats. Histopathologically, there were no abnormal changes in the testis, seminal vesicle or prostate in any rats dosed with Prograf, but intra-ductal eosinophilic globules, probably degeneration of the sperm cells, were observed in the epididymis of the 3 mg/kg/day group. Sperm counts and motility returned to the control levels after stopping of the drug. The results indicate that Prograf decreased sperm counts and motility through direct action on the sperm in the epididymis, but not the production of sperm in the testis. Cyclosporine A (CsA) was used as the reference drug in the present study. Thirty mg/kg/day of CsA also decreased sperm counts and motility, and stopping of the drug led to the recovery of these changes. The males dosed with Prograf for 2 weeks were mated with non-dosed females to investigate its effect on the fertility potential of the males. Prograf did not affect copulation or fertility index, but a decrease in the number of live fetuses associated with implantation loss was observed in the 3 mg/kg/day group. The changes were considered to be due to the decrease of sperm counts and motility, although 1 mg/kg/day of Prograf, 5-10 times the clinical dose, did not affect any fertility parameters including implantation index.
Hisatomi
A
A
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
Fujihira
S
S
Fujimoto
Y
Y
Fujii
T
T
Mine
Y
Y
Ohara
K
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D005260:Female; D005298:Fertility / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000097:blood; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D051381:Rats; D012098:Reproduction / Q000187:drug effects; D012669:Seminal Vesicles / Q000187:drug effects; D013076:Sperm Count / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D016559:Tacrolimus / Q000633:toxicity*; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood
D007166:Immunosuppressive Agents; D013739:Testosterone; D016572:Cyclosporine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016559:Tacrolimus