Effects of metformin on the rat testes: a light and electron microscopic study

Metformin, which is a biguanid antidiabetic drug, is commonly used in the treatment of Type 2 diabetic patients. Studies on the effects of the drug are usually focused on gestational diabetes and polycystic ovary syndrome with together increasing drug usage also involved with the treatment of diseases which in the pathogenesis of insulin resistance. There has been a few studies in the literature which examined the effects of metformin on male reproductive system and no ultrastructural study was found. In our study we aimed to evaluate the testicular tissue obtained from rats exposed to metformin treatment at different doses at light and electron microscopic level in comparison with biochemical data and demonstrate the histological changes in testicular tissue. In our study, twenty-six adult male Wistar albino rats weighing 250-300 g were used. The first group served as a control and was given distilled water. The second group received metformin at a dose of 150 mg/kg body weight/ day and the third group received metformin at a dose of 300 mg/kg body weight/ day by oral gavage for 30 days. At the end of the experiment testicular tissues were taken for light and electron microscopic examination and intra-cardiac blood samples were collected for biochemical analysis. In the experimental groups evaluated with light and electron microscopies, irregular seminiferous tubules, disruption of epithelial integrity, the decrease in spermatogenic cells, dilated intercellular spaces and degenerative changes in epithelium were observed relating to doses. Morphometric measurements of tubule diameters and epithelial heights and FSH, LH, testosterone, SOD and MDA data were evaluated and there were no statistically significant differences between groups. This study is of great importance because it is the first study to evaluate the effects of metformin on testis as ultrastructurally and the findings showed that high dose metformin may affect the structure of seminiferous tubules and spermatogenesis, however was thought these changes to be reversible. In addition, ıt was concluded that the effects of long-term using of metformin to be examined in detail with further studies on biochemical, molecular and immunohistochemical levels.