Antifertility effects of fluphenazine in adult male rats

Abstract

The underlying mechanisms in human infertility associated with hyperprolactinemia have yet to be established. Hyperprolactinemia is a known side-effect of fluphenazine, a broad spectrum, long-acting phenothiazine known to be D2 dopamine receptor antagonist. Dose-related effects of fluphenazine decanoate were ascertained on the fertility of 60-day treated, adult male rats. Significant increase in the serum levels of prolactin and decrease in the levels of LH and FSH were seen at doses of 1-3 mg/kg/day. No effect was evident on the serum testosterone (T) and estradiol. The tissue levels of Inhibins were not affected. The weights of testes, epididymides, seminal vesicles, ventral prostate, adrenal and pituitary glands were not affected. Testicular histology showed sloughing indicating the sensitivity of this parameter to FSH deficiency. Mating occurred within 10 days of cohabitation in the control and 1-2 mg/kg/day treated groups but delayed in the 3 mg/kg/day treated group with a significant effect on potency. Implantation sites, litter size and fertility index were significantly reduced at 2-3 mg/kg/day doses of fluphenazine. No effects however were seen on sperm counts or motility whereas morphological changes were apparent in the acrosome. Chromatin decondensation in vitro was enhanced and sperm chromatin structure assay revealed DNA denaturation. Hypothalamic tyrosine hydroxylase levels were increased in 1-3 mg/kg/day dose range. Hyperprolactinemic males sired fewer pups as compared to controls. Hypothalamic tyrosine hydroxylase was upregulated at all the doses. The antifertility effects of fluphenazine-induced hyperprolactinemia appeared to be unrelated to testosterone (T). In addition, FSH decrease might have affected the intrinsic sperm quality and thereby reduced litter size.