https://doi.org/10.4081/aiua.2025.14142
Guarding masculinity: telmisartan and aerobic exercise preserve testicular histomorphometry in diabetic rats
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 30 September 2025
Background: diabetes mellitus (DM) is associated with testicular damage, leading to male infertility. This study investigates the effects of telmisartan, moderate-intensity aerobic exercise, and their combination on testicular histopathology in a streptozotocin-induced diabetic rat model.
Methods: male Wistar rats were divided into five groups: healthy control (K0), diabetic control (K1), telmisartan monotherapy (K2), aerobic exercise monotherapy (K3), and combination therapy (K4). Diabetes was induced using streptozotocin (STZ), and treatments were administered for 10 weeks. Testicular histopathology was assessed by evaluating Johnsen score, Sertoli cell count, Leydig cell count, and seminiferous tubule diameter.
Results: diabetic rats (K1) showed significant declines in Johnsen score, Sertoli and Leydig cell counts, and seminiferous tubule diameter (p<0.05). Telmisartan (K2) and combination therapy (K4) significantly improved all parameters, with values approaching those of healthy controls (K0). Aerobic exercise (K3) improved seminiferous tubule diameter but had limited effects on Johnsen score, Sertoli, and Leydig cells. Kruskal- Wallis, Mann-Whitney U, ANOVA, Games-Howell, and LSD tests confirmed these findings.
Conclusions: Telmisartan, either as monotherapy or in combination with moderate-intensity aerobic exercise, effectively ameliorates testicular damage in diabetic rats. Aerobic exercise alone has a partial protective effect. These findings suggest potential therapeutic strategies for preventing diabetes-induced male infertility.
Downloads
1. Adelati S, Juniarto AZ, Miranti IP. [Histopatologi spermatogenesis testis tikus Wistar diabetes melitus - Histopathology of spermatogenesis of testis of diabetic Wistar rats].[Article in Indonesian]. J Kedokt Diponegoro. 2016;5:1760-9. Available from: https://media.neliti.com/media/publications/138794-ID-histopatologi-spermatogenesis-testis-tik.pdf
2. Vale A, Santos G, Silva T, et al. Influence of the AT1 receptor antagonists telmisartan and losartan on reproduction and offspring after paternal exposure to ionizing radiation. Reprod Sci. 2019;26:639-48. DOI: https://doi.org/10.1177/1933719118783251
3. Lotti F, Maggi M. Effects of diabetes mellitus on sperm quality and fertility outcomes: clinical evidence. Andrology. 2023; 11:399-416. DOI: https://doi.org/10.1111/andr.13342
4. Kushwaha S, Jena GB. Telmisartan ameliorates germ cell toxicity in the STZ-induced diabetic rat: studies on possible molecular mechanisms. Mutat Res Genet Toxicol Environ Mutagen. 2013; 755:11-23. DOI: https://doi.org/10.1016/j.mrgentox.2013.04.013
5. Toprak V, Akalın SA, Öcal E, et al. Histopathological examination of the protective effect of intense exercise in apoptotic germ cell damage due to diabetes. Acta Cir Bras. 2023; 38:e2023423. DOI: https://doi.org/10.1590/acb381423
6. Alves MG, Martins AD, Cavaco JE, et al. Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function. Tissue Barriers 2013;1:e23992. DOI: https://doi.org/10.4161/tisb.23992
7. Gumustekin M. HGF/c-met pathway has a role in testicular damage in diabetes induced by streptozotocin. Acta Endocrinol (Bucharest). 2017;13:17-22. DOI: https://doi.org/10.4183/aeb.2017.17
8. Aghamiri SM, Eslami Farsani M, Seyedebrahimi R, et al. Synergic effects of rosemary extract and aerobic exercise on sperm parameters and testicular tissue in an aged rat model. Gene Cell Tissue. 2023; 10: e130832 DOI: https://doi.org/10.5812/gct-130832
9. Santillo A, Giacco A, Falvo S, et al. Mild exercise rescues steroidogenesis and spermatogenesis in rats submitted to food withdrawal. Front Endocrinol (Lausanne). 2020; 11:302. DOI: https://doi.org/10.3389/fendo.2020.00302
10. Amaral LSB, Souza CS, Lima HN, Soares TJ. Influence of exercise training on diabetic kidney disease: a brief physiological approach. Exp Biol Med (Maywood). 2020; 245:1142-54. DOI: https://doi.org/10.1177/1535370220928986
11. Kraemer WJ, Ratamess NA, Volek JS, et al. The effects of amino acid supplementation on hormonal responses to resistance training overreaching. Metabolism. 2006; 55:282-91. DOI: https://doi.org/10.1016/j.metabol.2005.08.023
12. Sato-Horiguchi C, Ogawa D, Wada J, et al. Telmisartan attenuates diabetic nephropathy by suppressing oxidative stress in mice. Nephron Exp Nephrol. 2013; 121:97-108. DOI: https://doi.org/10.1159/000343102
13. Ballester J, Muñoz MC, Domínguez J, et al. Insulin-dependent diabetes affects testicular function by FSH- and LH-linked mechanisms. J Androl. 2004;25:706-19. DOI: https://doi.org/10.1002/j.1939-4640.2004.tb02845.x
14. Imenshahidi M, Roohbakhsh A, Hosseinzadeh H. Effects of telmisartan on metabolic syndrome components: a comprehensive review. Biomed Pharmacother. 2024; 171:116169. DOI: https://doi.org/10.1016/j.biopha.2024.116169
15. Guo Z, Yan X, Wang L, et al. Effect of telmisartan or insulin on the expression of adiponectin and its receptors in the testis of streptozotocin-induced diabetic rats. Horm Metab Res. 2016; 48:404-12. DOI: https://doi.org/10.1055/s-0042-101549
16. Fouad AA, Albuali WH, Al-Mulhim AS, Jresat I. Protective effect of telmisartan treatment against arsenic-induced testicular toxicity in rats. Z Naturforsch C J Biosci. 2015; 70:175-81. DOI: https://doi.org/10.1515/znc-2015-5031
17. Maleki S, Azarbayjani MA, Malayeri SR, et al. The effect of aerobic exercise and ethanolic extract of rice bran on gene expression in rat liver. Health Nexus 2024; 2:89-100. DOI: https://doi.org/10.61838/kman.hn.2.3.11
18. Samadian Z, Tofighi A, Razi M, et al. Effect of moderate-intensity exercise training on GDNF signaling in diabetic rat testes. Diabetes Res Clin Pract. 2020; 167:108332. DOI: https://doi.org/10.1016/j.diabres.2020.108332
19. Arafa M, Elbardisi H, Majzoub A. Sperm retrieval in ejaculatory dysfunction. In: Majzoub A, Agarwal A, Esteves SC, editors. The complete guide to male fertility preservation. Cham: Springer; 2018. p. 43-56. DOI: https://doi.org/10.1007/978-3-319-42396-8_4
20. Barzilay JI, Gao P, Rydén L, et al. Effects of telmisartan on glucose levels in people at high risk for cardiovascular disease but free from diabetes: the TRANSCEND study. Diabetes Care 2011; 34:1902-7. DOI: https://doi.org/10.2337/dc11-0545
21. Widodo EY, I’tishom R, Purwanto B. [Potensi ekstrak rumput kebar dalam mempertahankan jumlah sel Sertoli mencit model diabetes melitus - The potential of kebar grass extract in maintaining the number of Sertoli cells in mice with diabetes mellitus model].[Article in Indonesian]. J Peneliti Kesehatan Suara Forikes. 2020; 11:277-82. DOI: https://doi.org/10.33846/sf11311
22. Chigurupati S, Son TG, Hyun DH, et al. Lifelong running reduces oxidative stress and degenerative changes in the testes of mice. J Endocrinol 2008;199:333-41. DOI: https://doi.org/10.1677/JOE-08-0306
How to Cite

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.