Effects of vildagliptin on the pituitary– gonadal axis of male wistar rats
This study investigated the effects of daily administration of Vildagliptin (an oral anti-diabetic drug) for eight weeks on some sperm parameters, pituitary as well as gonadal hormones, litter size and testicular with epididymal histology of male Wistar rats. A total of 60 male and 40 female Wistar rats weighing 120 - 150 g were used for the study. The 60 male rats were divided into 3 equal categories (A, B and C). Each category was further divided into 4 groups (making a total of 12 groups), with each group containing 5 rats. In category A, Group 1, the control group, received 1.4 ml/kg of distilled water daily for 8 weeks; while Groups 2, 3, and 4 received 0.35 mg/kg, 0.70 mg/kg and 1.4 mg/kg of Vildagliptin (orally) daily for 8 weeks respectively. Thereafter, the rats were sacrificed to determine the following parameters: sperm characteristics (count, motility, viability and morphology), serum testosterone, follicle-stimulating hormone and luteinizing hormone concentrations. Histology of the testis and epididymis was done. In category B, Group 5, the control group, received 1.4 ml/kg of distilled water daily for 8 weeks via oral route; while Groups 6, 7, and 8 received 0.35 mg/kg, 0.70 mg/kg and 1.4 mg/kg of Vildagliptin (orally) daily for 8 weeks respectively. Thereafter, each male rat was allowed to cohabit (so as to mate) with 2 apparently healthy non-pregnant female rats in separate cages. The litter sizes were determined and summed up for each group. In category C, Group 9, the control group, received 1.4 ml/kg of distilled water daily for 8 weeks; while Groups 10, 11, and 12 received 0.35mg/kg, 0.70 mg/kg and 1.4 mg/kg of Vildagliptin (orally) daily for 8 weeks respectively. All the rats were allowed another 8 weeks of drug-free recovery period. Subsequently, they were sacrificed and the same parameters (as listed for category A) were determined. The results of the study showed a dose-independent but partly reversible significant decrease in the sperm counts (X 106 /ml) of all the Vildagliptin-treated groups when compared with the control (F=3.89, p=0.045). There was a dose-independent but reversible significant reduction in the sperm motility (%) of the treated groups when compared with the control (F=9.84, p=0.0015). There was a dose-independent but reversible significant increase in the percentage of sperms with abnormal morphology in the treated groups when compared with the control (F=4.39, p=0.026). However, there was no significant change in sperm viability (F=1.00, p=0.43). There was a dose-independent significant decrease in serum testosterone (F=4.51, p=0.040) and significant increase in serum FSH (F=4.39, p=0.037) as well as delayed significant increase in LH (F=4.39, p=0.037) of the treated rats when compared with the control. There was a highly significant dose-dependent decrease in the litter size of treated rats when compared with the control (F=18.66, p<0.0001). There was no visible deleterious effect on the histoarchitecture of the testes of the treated rats, however there was a dose-dependent distortion in the histoarchitecture of the epididymis of the rats in the treated groups when compared with the control and these were largely reversible after 8 weeks of recovery. In conclusion, Vildagliptin adversely affected the reproductive structure and function of male Wistar rats. It caused significant deleterious effects on the sperm counts, motility, morphology, epididymal histology as well as the serum testosterone, FSH and LH with resultant decrease in litter size. Further studies will be required to characterize these effects at the molecular level and to devise the means of mitigating the effects.