The Ultrastructural Changes of the Sertoli and Leydig Cells Following Streptozotocin Induced Diabetes

Document Type: Original Article

Authors

1 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

2 Department of Basic Sciences, Histology and Embryology Sections, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

Abstract

Objective(s)
This investigation was conducted to evaluate the effects of diabetes on the structure and function of testicular tissue.
Materials and Methods
Diabetes was induced in male adult rats by a single intraperitoneal injection of streptozotocin. Body and testicular weight, hormonal analyses, histological and ultrastructural analyses were measured.
Results
The body and testicular weights were dropped significantly (P< 0.05) in diabetic rats in comparison with control rats. On the other hand, in diabetic rats, the blood glucose level increased significantly (P< 0.05). The blood plasma levels of testosterone, 17-β estradiol, progesterone, FSH and LH were reduced in diabetic rats. Histomorphological studies were revealed reduction in diameter of seminiferous tubules and germinal epithelium height, edema in interstitial tissue, germ cell depletion, decrease in cellular population and activity with disruption of spermatogenesis in diabetic rats. Ultrastructural study showed the mitochondrial change and reduction of smooth endoplasmic reticulum in Sertoli and presence of lipid droplets in Leydig cells of diabetic rat’s testes.
Conclusion
The results of the present study confirmed that, the ultrastructural changes of Sertoli and Leydig cells, brought about by streptozotocin induced diabetes, because of the alterations in pituitary gonadotropins, and these changes influence the normal spermatogenesis in rats.

Keywords


1. Yanardag R, Ozsoy-Sacan O, Bolkent S, Orak H, Karabulut-Bulan O. Protective effects of metformin treatment on the liver injury of streptozotocin-diabetic rats. Hum Exp Toxicol 2005; 24: 129-135.

2. Cai L, Chen S, Evans T, Xi Deng D, Mukherjee K, Chakrabarti S. Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism. Urol Res 2000; 28: 342-347.

3. Orth JM, Murray FT, Bardin CW. Ultrastructural changes in Leydig cells of streptozotocin-induced diabetic rats. Anat Rec 1979; 195:415-430.

4. Kuhn-Velten N, Waldenburger D, Staib W. Evaluation of steroid biosynthetic lesions in isolated Leydig Cells from the testes of streptozotocin-diabetic Rats. Diabetology 1982; 23: 529-533.

5. Morimoto S, Mendoza-Rodriguez CA, Hiriat M, Larrieta ME, Vital P, Cerbon MA. Protective effect of testosterone on early apoptotic damage induced by streptozotocin in rat pancreas. J Endocrinol  2005; 187:217-224.

6. Oksanen A. Testicular lesions of streptozotocin diabetic rats. Horm Res 1975; 6:138-144.

7. Ballester J, Carmen Munoz M, Dominguez J, Rigau T, Guinovart JJ, Rodriguez-Gil J. Insulin-dependent diabetes affect testicular function by FSH- and LH-linked mechanisms. J Androl  2004; 25:706-719.

8. Ward DN, Bousfield GR, Moore KH. Gonadotropins. Reproduction in domestic animals. San Diego: California Academic Press; 1991. p.25-67.

9. Tesone M, Oliviera-Filho RM, Biella de Souza Valle L, Calvo JC, Baranao JLS, Foglia VG, et al. Androgen receptors in the diabetic rat. Diabetol 1980; 18:385-390.

10. Ozdemir O, Akalin PP, Baspinar N, Hatipoglu F. Pathological changes in the acute phase of streptozotocin-induced diabetic rats. Bull Vet Inst Pulawy  2009; 53:783-790.

11. Guneli E, Tugyan K, Ozturk H, Gumustekin M, Cilaker S, Uysal N. Effect of melatonin on testicular damage in streptozotocin-induced diabetes rats. Eur Surg Res  2008; 40:354-360.

12. Navarro-Cassado L, Juncos-Tobarra MA, Chafer-Rudilla M, Iniguez de Onzono L, Blazquez-Cabrera JA, et al. Effect of experimental diabetes and STZ on male fertility capacity. Study in rats. J Androl  2010; 108:007260.

13. Cameron DF, Murray FT, Drylie DD.Interstitial compartment pathology and spermatogenic disruption in testes from impotent diabetic men. Anat  Rec  1985; 213:53-62.

14. Steger RW, Rabe M. The effect of diabetes mellitus on endocrine and reproductive function. Proc Soc Exp Biol Med 1997; 214:1-11.

15. Venkateswaran S, Pari L. Antioxidant effect of Phaseolus vulgaris in streptozotocin-induced diabetic rats. Asia Pac J Clin Nutr  2002; 11:206-209.

16. Shetty G, Wilson G, Huhtaniemi I, Shuttlesworth GA, Reissmann T, Meistrich ML. Gonadotropin releasing hormone analogs and testosterone inhibits the recovery of spermatogenesis in irradiated rats. Endocrinology  2000; 141:1735-1745.

17. Andulla B, Varadacharyulu NCh. Antioxidant role of mulberry leaves in streptozotocin-diabetic rats. Clin Chim Acta  2003; 338:3-10.

18. Hunt EL, Baily DW. The effects of alloxan diabetes on the reproductive system of young male rats. Acta Endocrinol 1961; 38:432- 440.

19. Howland BE, Zebrowski EJ. Serum and pituitary gonadotropins levels in alloxan-diabetic rats. Horm  Metab Res 1974; 6: 121-124.

20. Kuhn-Velten N, Schermer R, Staib W. Effect of streptozotocin-induced hyperglycemia on androgen-binding protein in rat testis and epididymis. Diabetol 1984; 26:300-303.

21. Paz-Frenkel G, Homonnai ZT, Drasnin N, Sofer A, Kaplan R, Kraicer PF. Fertility of the streptozotocin-diabetic male rat. Andrologia 1978; 10:127-136.

22. Paz-Frenkel G, Homonnai ZT, Harell A, Kraicer PF. Improvement in the fertility of streptozotocin-diabetic male rats following treatment with insulin and human chorionic gonadotropin. Isr J Med Sci 1978; 14: 1073-1078.

23. Calvo JC, Valle LBS, Baranao JL, Teson M, Charreau EH. NADPH generating enzymes in Leydig cells from diabetic rats. Horm Metab Res 1979; 11:161-164.

24. Jackson FL, Hutson JC. Altered responses to androgen in diabetic male rats. Diabetes 1984; 33: 819-824.

25. Murray FT, Cameron DF, Vogel RB, Thomas RG, Wyss HU, Zauner CW. The pituitary-testicular axis at rest and dring moderate exercise in male with diabetes mellitus and normal sexual function. J Androl 1988; 9:197-206.

26. Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab  2005; 90:2636-2641.

27. Hutson JC, Stocco DM, Campbell GT, Wagoner J. Sertoli cell function in diabetic, insulin treated diabetic, and semi starved rats. Diabetes 1983; 32:112-116.

28. Sudha S, Valli G, Mary Julie P, Arunakaran J, Govindarajulu P, Balasu-Bramanian K. Influence of streptozotocin-induced diabetes and insulin treatment on the pituitary-testicular axis during sexual maturation in rat. Endocrinol Diabetes 1999; 107:14-20.

29. Khaki A, Nouri M, Fathiazad F, Ahmadi-Ashtiani HR, Rastgar H, Rezazadeh S. Protective effect of quercetin on spermatogenesis in streptozotocin-induced diabetic rat. J Med Plan. 2009; 8:57-64.

30. Cameron DF, Orth J, Murray FT. Morphological alteration in the testes from diabetic man and rat. Diabetes 1982; 31: 11A.

31. Rossi GI, Aeschlimann M. Morphometric studies of pituitary gland and testes in rats with streptozotocin-induced diabetes. Andrologia 1982; 14:532-542.

32. Hassan G, Abdel Moneium T. Structural changes in the testes of streptozotocin-induced diabetic rats. Suez Canal Univ Med J. 2001; 4:17-25.

33. Williamson JR, Kilo C. Capillary basement membranes. Diabetes 1983; 32:96-100.

34.Anderson JE, Jones D, Penner SB, Thilveris JA. Primary hypoandrogenism in experimental diabetes in the Long-Evans rats. Diabetes 1987; 36:1104-1110.

35. Sanguinetti RE, Ogawa K, Kurohmaru M, Hayashi I. Ultrastructural changes in mouse Leydig cells after streptozotocin administration. Exp Anim 1995; 44:71-73.

36. Oztürk F, Gül M, Agkadir M, Yagmurca M. Histological alterations of rat testes in experimental diabetes. T Kin J Med Sci 2002; 22: 173-178.

37. Abdul – Ghani MA, Defronzo R. Mitochondrial dysfunction in type 2 diabetes-an update. US Endocrinol  2008; 28-31.

38. Robinson R, Fritz I B. Metabolism of glucose by Sertoli cells in culture. Biol Reprod 1981; 24:1032-1041.

39. Jegou B. The Sertoli cell. Bailliere's Clin Endocrinol Metabol  1992; 6:273-311.

40. Hutson JC. Altered biochemical responses by rat Sertoli cells and peritubular cells  cultured under stimulated diabetic conditions. Diabetologia 1984; 26:155-158.