Effects of quercetin on spermatogenesis and steroidogenesis in intact and orchidectomized rats

Abstract

This thesis reports the effects of quercetin, a flavonoid found in many plant species including Thai herb used for sexual dysfunction treatment, on spermatogenesis and steroidogenesis of male rats. Effects of quercetin on spermatogenesis and steroidogenesis were first studied in the intact male Sprague-Dawley rats. Eight weeks old rats were subcutaneously injected with quercetin at dose of 0 (Q0), 30 (Q30), 90 (Q90) or 270 (Q270) mg/kgBW/day for 3, 7 or 14 days, and 28-day treatments were performed additionally with Q0 and Q90 rats. The results showed that effects of quercetin on reproductive organs (testes, epididymis-vas deferens, prostate gland and seminal vesicle), sex hormones (testosterone, LH and FSH) and sperm quality (sperm concentration, viability and mobility) depend on dose and duration of treatment. The shortest time of quercetin treatment (3 days) at any dosage had no effects on reproductive organ weights and histological alterations and sperm quality. However, the prolonged (7, 14 and 28 days) and higher doses (Q90 and Q270) treatments affected the reproductive parameters. The weights of the testes and epididymis-vas deferens and sperm quality of Q270 (day 7 and 14) and Q90 (day 14 and 28) were significantly increased, while weights of prostate gland and seminal vesicle were significantly decreased. The weight changes were associated with the histological alterations of sex organs, while the increased sperm quality was related to the increased weights of testis and epididymis via the distribution of sperm and fluid. Serum LH levels (Q90 at day 7, 14 and 28; Q270 at day 3, 7 and 14) FSH levels (Q90 at day 7 and 28; Q270 at day 7 and 14) and testosterone levels (Q270 at day 3 and 14) were significantly decreased. The expression of mRNA of StAR protein and P450scc were not significantly changed after quercetin treatment, except that of the Q90 rats at day 28 which showed a reduced expression of P450scc. The decreased testosterone levels which associated with the reduced levels of serum LH and FSH, but not the Leydig cell steroidogenesis, indicated that quercetin may have an androgenic activity to suppress HPG axis. Effects of quercetin on fertility were further studied in male rats subcutaneously injected with Q0, Q90 or Q270 for 14 days, and Q0 or Q90 for 28 days. During the last five day of treatment (day 10-14 or day 24-28), the treated male rat was housed with two virgin untreated female rats. Although there were no changes of fertility indexes (or the male ability to mate with virgin female) in Q90 rats even that the treatment was prolonged to 28 days, the percentage of male with sperm positive female was significantly increased. Fertility indexes, percentage of male with sperm positive female, number of pregnant females, and number of fetus per litter were significantly decreased in Q270 rats of 14-day treatment. The reduced fertility in the treated rats may be associated with changes in weight and histology of prostate gland and seminal vesicle and the reduced testosterone levels. Actions of quercetin on reproductive organs and sex hormone levels were studied in orchidectomized (ODX) rats. The rats were subcutaneously injected with Q0, Q30, Q90 or Q270 or 1 mg/kgBW/day of testosterone proprionate (Tp) for 14 days. Sham group was subcutaneously injected with vehicle (20% glycerol). After ODX for 14 days, the rats showed increased FSH and LH levels, decreased testosterone levels and decreased weights of epididymis-vas deferens, prostate gland and seminal vesicle compared to the sham rats. Although Tp treatment could recover these effects, these changes were not recovered after quercetin treatment. The result indicates that quercetin may have very low or no androgenic activity in ODX rats. Overall results suggest that quercetin may exhibit its androgenic activity by potentiating endogenous androgens or through other mechanisms such as the antioxidant effects. Based on these results, the use of quercetin (at Q90) as a drug for treatment of male infertility should be considered.