Metformin Reduces the Extent of Varicocele-Induced Damage in Testicular Tissue

Abstract

Varicocele is a medical condition where retrograde flow of blood leads to increased hydrostatic pressure in testicular veins and the prevalence of varicocele is predicted to vary between 30 to 40% in infertile men. Metformin, major therapeutic agent in the treatment of type 2 diabetes mellitus, was shown to reduce oxidative stress and apoptosis in renal tubular epithelial cells and testis of animal models. However potential protective effects of metformin against varicocele-induced testicular damage has not been studied. We investigated the impact of metformin on spermatogenesis assessed with Johnsen score, seminiferous tubule integrity and apoptotic activity assessed with the expression of cleaved caspase 3 activity. A total of 36 male Wistar rats (6-week-old) were divided into six groups (n=6 for each group); (C) control group, S (sham group), V (varicocele-only group), V+M (varicocele + metformin group), V/E (varicocele + varicocelectomy group), V/E+M (varicocele + varicocelectomy + metformin group). Metformin administration improved spermatogenesis, seminiferous tubule integrity and reduced apoptotic activity as manifested by the decreased expression of cleaved caspase 3 in rats with varicocele. However, metformin did not exhibit any additional benefit on these parameters in varicocelectomies rats. As conclusion, metformin treatment reduced the extent of damage to spermatogenesis in rats with varicocele, although no additional benefit was detected when administered following varicocele surgery.