Journal of Basic and Clinical Pathophysiology

Journal of Basic and Clinical Pathophysiology

Metformin improves semen profile and hormonal levels in experimental varicocele in the rat

Document Type : Research Paper

Authors
Hooman Karimi 1
Ahmad Asghari 1
Alireza Jahandideh 1
Ghasem Akbari 1
Pejman Mortazavi 2
1 Department of Clinical Science, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 Department of Pathobiology, Science and Research Branch, Islamic Azad University, Tehran, Iran
10.22070/jbcp.2023.18013.1171
Abstract
Abstract
Objective: This study aimed to determine the effect of metformin (MET) on semen profile and hormonal levels in a model of varicocele in rats.
Materials and Methods: Sixty male Wistar rats were allocated into 5 treatment groups as control and varicocele groups. In groups 3-5, varicocele animals received MET (25, 50 and 100 mg/kg) for 42 days. At the end of the study, semen evaluations and serum testosterone and luteinizing hormone and follicle stimulating hormone levels were measured.
Results: Experimental varicocele significantly decreased total sperm count and sperm motility and increased non-motile sperms compared to the control group (p<0.05). Metformin administration (50 and 100 mg/kg) significantly increased total sperm count and sperm motility and decreased non-motile sperm as compared to the varicocele group (p<0.05). In addition, experimental varicocele significantly decreased testosterone and luteinizing hormone and follicle stimulating hormone levels as compared to the control group (p<0.05). Metformin administration (50 and 100 mg/kg) significantly increased testosterone and luteinizing hormone and follicle stimulating hormone levels as compared to the varicocele group (p<0.05).
Conclusion: These results suggested that metformin has positive role against varicocele in the rat.
Keywords
Metformin
Semen
Testosterone
Luteinizing hormone
Follicle stimulating hormone
Varicocele
  1. Adaramoye O, Akanni O, Adesanoye O, Labo-Popoola O, Olaremi O. Evaluation of toxic effects of metformin hydrochloride and glibenclamide on some organs of male rats. Nigerian journal of physiological sciences. 2012;27(2):137-44.
  2. Attia SM, Helal GK, Alhaider AA. Assessment of genomic instability in normal and diabetic rats treated with metformin. Chemico-biological interactions. 2009 Jul 15;180(2):296-304.
  3. Badkoobeh P, Parivar K, Kalantar SM, Hosseini SD, Salabat A. Effect of nano-zinc oxide on doxorubicin-induced oxidative stress and sperm disorders in adult male Wistar rats. Iranian journal of reproductive medicine. 2013 May;11(5):355.
  4. Banihani SA. Effect of metformin on semen quality. Brazilian Journal of Pharmaceutical Sciences. 2016 Oct;52:591-4.
  5. Banihani SA. Effect of metformin on semen quality. Brazilian Journal of Pharmaceutical Sciences. 2016 Oct;52:591-4.
  6. Bertoldo MJ, Guibert E, Tartarin P, Guillory V, Froment P. Effect of metformin on the fertilizing ability of mouse spermatozoa. Cryobiology. 2014 Apr 1;68(2):262-8.
  7. Bosman E, Esterhuizen AD, Rodrigues FA, Becker PJ, Hoffmann WA. Effect of metformin therapy and dietary supplements on semen parameters in hyperinsulinaemic males. Andrologia. 2015 Nov;47(9):974-9.
  8. Briffa J, Sinagra E, Blundell R. Heavy metal pollution in the environment and their toxicological effects on humans. Heliyon. 2020 Sep 1;6(9).
  9. Cahova M, Palenickova E, Dankova H, Sticova E, Burian M, Drahota Z, Cervinkova Z, Kucera O, Gladkova C, Stopka P, Krizova J. Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2015 Jul 15;309(2):G100-11.
  1. Celik-Ozenci C, Bayram Z, Akkoyunlu G, Korgun ET, Erdogru T, Seval Y, Ustunel I, Baykara M, Demir R. Localization of NGF and nNOS in varicocele-induced rat testis. Acta histochemica. 2006 Feb 20;107(6):435-42.
  2. Ergani B, Eyiol A, Karabiçak M, Gitmez M, Körez MK. Echocardiographic and hemodynamic changes in patients with high-grade varicocele. Biomolecules and Biomedicine. 2023 Jun 6;23(3):510.
  3. Froment P. The insulin sensitiser metformin regulates chicken Sertoli and germ cell populations. Reproduction. 2016;151:527-38.
  4. Fuschi A, Capone L, Abuorouq S, Al Salhi Y, Velotti G, Aversa S, Carbone F, Maceroni P, Petrozza V, Carbone A, Pastore AL. Shear wave elastography in varicocele patients: prospective study to investigate correlation with semen parameters and histological findings. International Journal of Clinical Practice. 2021 Mar;75(3):e13699.
  5. Hedaiaty M. Administration of metformin in clinical medicine; an updated mini-review on current findings. Journal of Nephropharmacology. 2018 Jan 20;7(2):61-5.
  6. Hollander-Cohen L, Golan M, Levavi-Sivan B. Differential regulation of gonadotropins as revealed by transcriptomes of distinct LH and FSH cells of fish pituitary. International Journal of Molecular Sciences. 2021 Jun 17;22(12):6478.
  7. Huang X, Zhang C, Hu R, Li Y, Yin Y, Chen Z, Cai J, Cui F. Association between occupational exposures to pesticides with heterogeneous chemical structures and farmer health in China. Scientific Reports. 2016 Apr 27;6(1):25190.
  8. Jana K, Jana S, Samanta PK. Effects of chronic exposure to sodium arsenite on hypothalamo-pituitary-testicular activities in adult rats: possible an estrogenic mode of action. Reproductive biology and endocrinology. 2006 Dec;4:1-3.
  9. Karimi H, Asghari A, Jahandideh A, Gh A, Mortazavi P. Effects of Metformin on Experimental Varicocele in Rats. Archives of Razi Institute. 2021;76(2):371.
  1. Masterson TA, Turner D, Vo D, Blachman-Braun R, Best JC, Westfield G, Bryson N, Ramasamy R. The effect of longer-acting vs shorter-acting testosterone therapy on follicle stimulating hormone and luteinizing hormone. Sexual Medicine Reviews. 2021 Jan;9(1):143-8.
  2. Mawhinney M, Mariotti A. Physiology, pathology and pharmacology of the male reproductive system. Periodontology 2000. 2013 Feb;61(1):232-51.
  3. Morgante G, Tosti C, Orvieto R, Musacchio MC, Piomboni P, De Leo V. Metformin improves semen characteristics of oligo-terato-asthenozoospermic men with metabolic syndrome. Fertility and sterility. 2011 May 1;95(6):2150-2.
  4. Nishimura H, L’Hernault SW. Spermatogenesis. Current Biology. 2017 Sep 25;27(18):R988-94.
  5. Nna VU, Bakar AB, Ahmad A, Umar UZ, Suleiman JB, Zakaria Z, Othman ZA, Mohamed M. Malaysian propolis and metformin mitigate subfertility in streptozotocin-induced diabetic male rats by targeting steroidogenesis, testicular lactate transport, spermatogenesis and mating behaviour. Andrology. 2020 May;8(3):731-46.
  6. Pourheydar B, Azarm F, Farjah G, Karimipour M, Pourheydar M. Effect of silymarin and metformin on the sperm parameters and histopathological changes of testes in diabetic rats: An experimental study. International Journal of Reproductive BioMedicine. 2021 Dec;19(12):1091.
  7. Pourheydar B, Azarm F, Farjah G, Karimipour M, Pourheydar M. Effect of silymarin and metformin on the sperm parameters and histopathological changes of testes in diabetic rats: An experimental study. International Journal of Reproductive BioMedicine. 2021 Dec;19(12):1091.
  8. Sahin Z, Bayram Z, Celik-Ozenci C, Akkoyunlu G, Seval Y, Erdogru T, Ustunel I, Baykara M, Demir R. Effect of experimental varicocele on the expressions of Notch 1, 2, and 3 in rat testes: an immunohistochemical study. Fertility and sterility. 2005 Jan 1;83(1):86-94.
  9. Shpakov AO, Ryzhov JR, Bakhtyukov AA, Derkach KV. The regulation of the male hypothalamic-pituitary-gonadal axis and testosterone production by adipokines. InAdvances in testosterone action 2018 Nov 5 (pp. 25-57). IntechOpen.
  10. Tartarin P, Moison D, Guibert E, Dupont J, Habert R, Rouiller-Fabre V, Frydman N, Pozzi S, Frydman R, Lécureuil C, Froment P. Metformin exposure affects human and mouse fetal testicular cells. Human Reproduction. 2012 Nov 1;27(11):3304-14.
  1. Wang K, Hu H, Cui W, Zhang X, Tang Q, Liu N, Lan X, Pan C. Palliative effects of metformin on testicular damage induced by triptolide in male rats. Ecotoxicology and Environmental Safety. 2021 ;222:112536.
  2. Yan WJ, Mu Y, Yu N, Yi TL, Zhang Y, Pang XL, Cheng D, Yang J. Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet. Journal of assisted reproduction and genetics. 2015 Jul;32:1097-104.
  3. Zaidi AA, Khan MA, Sharif A, Shakir L, Irshad A, Ali A, Shaheryar ZA. Comparative study of sperm motility in Metformin-using and Insulin-dependent diabetics. Biomedical Research and Therapy. 2017 Jun 25;4(06):1388-99.
  4. Zimmermann, M., 1983. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16, 109-110.