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 decreased sperm counts and motility, but did not affect testosterone level in the serum of rats. Histopathologically, ther...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 1996-05, Vol.109 (2), p.75-83
Main Authors: Hisatomi, Akihiko, Fujihira, Shiro, Fujimoto, Yoshikatsu, Fujii, Toshiyuki, Mine, Yasuhiro, Ohara, Kaname
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Body Weight - drug effects
Cyclosporine - pharmacology
Drug toxicity and drugs side effects treatment
Epididymis - drug effects
Epididymis - pathology
Female
Fertility - drug effects
Fertility potent
Follicle Stimulating Hormone - blood
Immunosuppressive Agents - toxicity
Luteinizing Hormone - blood
Male
Medical sciences
Organ Size - drug effects
Pharmacology. Drug treatments
Prograf
Prostate - drug effects
Rats
Reproduction - drug effects
Seminal Vesicles - drug effects
Sperm Count - drug effects
Sperm counts and motility
Sperm Motility - drug effects
Spermatogenesis
Spermatogenesis - drug effects
Tacrolimus - toxicity
Testis - drug effects
Testis - pathology
Testosterone - blood
Toxicity: urogenital system
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Summary: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 decreased 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.
ISSN:0300-483X
1879-3185
DOI:10.1016/0300-483X(96)03312-4