Sitagliptin as a dipeptidyl peptidase-4 inhibitor is approved for the treatment of patients with type 2 diabetes. Despite its therapeutic effects, it induces oxidative stress and negatively impact reproduction. This study investigated the effect of myo-inositol, recognized for its antioxidant properties, on the quality of testicular tissue in diabetic mice treated with sitagliptin. Thirty adult male NMRI mice were divided into 5 groups (n=6): control group, diabetic group (150 mg/kg/day streptozotocin + 110 mg/kg/day nicotinamide), diabetic + sitagliptin group (30 mg/kg/day), diabetic + myo-inositol group (300 mg/kg/day), and diabetic + sitagliptin + myo-inositol group. After 35 days of treatment, the mice were dissected, and the left testis was isolated for stereological studies and evaluation of spermatogenesis indices. The volume of the testis, the volume of seminiferous tubules, the volume of interstitial tissue, the length, diameter, height of the germinal epithelium, and the thickness of the basement membrane in the seminiferous tubules, as well as the number of spermatogenic cells, Sertoli cells, and Leydig cells, spermatogenesis indices and Jansen score showed a significant decrease in the diabetic group compared to the control group (p<0.05). In the diabetic + sitagliptin group, there was no significant difference in these parameters compared to the diabetic group (p>0.05). These adverse effects were compensated in the diabetic + sitagliptin + myo-inositol group compared to the diabetic + sitagliptin group. The results indicated that co-administration of sitagliptin and myo-inositol improves the quality of testicular tissue, highlighting myo-inositol's potential protective role against sitagliptin- induced reproductive damage in diabetic mice.
