Effect of ivermectin on male fertility and its interaction with P-glycoprotein inhibitor (verapamil) in rats

Administration of permeability-glycoprotein (Pgp) inhibitors can modify the pharmacological properties or induce toxic effects of Pgp substrates. The effects of administration of ivermectin (anthelmentic drug, Pgp substrate), either alone or simultaneously with verapamil (Pgp inhibitor) on male fertility were studied by determining mounting behavior, epididymal spermatozoal analysis, weight and histopathological examination of male reproductive organs and cytogenetic evaluation of meiotic chromosome. The results revealed that administration of ivermectin once weekly for 8 weeks induced slight fertility disturbances. While, pre-treatment with verapamil disturbed male fertility through altering different sperm parameters and histological structure of reproductive organs. Cytogenetic study revealed partial effect of ivermectin on meiosis. Meanwhile, the combined treatment of ivermectin and verapamil induced stronger effects on germ cells, increased frequency of meiotic structural chromosomal aberrations and increased X–Y chromosomal dissociation, raising the attention to the genetic quality of mature sperm. We concluded that ivermectin has slight effects on male fertility, but when taken with verapamil induced adverse effects on meiosis and fertility.