Effect of a calcineurin inhibitor tacrolimus (FK506) treatment on meiotic chromosomes in testes, epididymal spermatozoa and fertility in Swiss Albino male mice

Abstract

Tacrolimus hydrate (FK506), isolated from Streptomyces tsukubaensis, is an immensely used immunosuppressive agent. It was evaluated for its effects on meiotic chromosomes in testes, epididymal spermatozoa and fertility in male mice. The study under different parameters constituted sub acute (seven days) administration (gavage) of FK506 at doses of 4, 8 and 16 mg/kg/day body weight. The results obtained in present study revealed that, FK506 significantly induced spermatozoa abnormalities, lowered
fertility and increased embryonic loss. The observed changes related to spermatogenic dysfunction reflected statistically significant increased aberrations in the meiotic chromosomes. These aberrations seemed to be induced by the inhibitory effect of the drug on the signal transduction pathways in the cells and interference in the transcription processes and proliferation of cells. Further studies are warranted to evaluate the safe dose and duration of therapy to determine the exact mode of action of FK506 induced germ cell toxicity.

Key words: Tacrolimus (FK506), sperm quality, germ cell toxicity, embryonic loss.