Introduction. Few oral antidiabetic drugs have been evaluated for their reproductive complication. This study aimed to evaluate the effect of metformin, pioglitazone and sitagliptin on the structure of male reproductive system through an immunohistopathological study.

Material and methods. Sprague-Dawley male rats were injected with streptozotocin. The diabetic rats were divided into four groups (n = 8/each group); diabetic control, metformin-, pioglitazone- and sitagliptin-treated groups in addition to a normal control group (n = 8). At the end of the experiment, blood samples were collected for biochemical assessment. Testis, epididymis and seminal vesicle were dissected and processed for histopathological examination using routine and immune-staining.

Results. All drugs significantly (p < 0.05) decreased fasting blood glucose, glycated hemoglobin, total cholesterol, triglycerides and malondialdehyde compared to the diabetic control group. Metformin has induced the least pathologic changes on the structure of the testis, epididymis and seminal vesicle among the studied drugs. Metformin succeeded to restore weights of testis, epididymis and seminal vesicle as well as testosterone hormone level back to values of the NC group while the pioglitazone and sitagliptin failed to do that. A significant reduction (p < 0.05) in testicular ERa and ERb immunoexpression of pioglitazone-treated group as well as suppression of ERb and AR immunoreactivity in in epididymus and seminal vesicles of pioglitazone- and sitagliptin-treated rats were observed compared to the control animals.

Conclusions. Histological structure as well ER and AR expression in the system organs were negatively and significantly affected with all studied drugs. Metformin has the least effect on the structure of the studied male reproductive organs. Thus, pioglitazone and sitagliptin treatment should be avoided in young male diabetic patients.