Volume 16, Issue 4 (April 2018)                   IJRM 2018, 16(4): 235-246 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Sampannang A, Arun S, Burawat J, Sukhorum W, Iamsaard S. Testicular histopathology and phosphorylated protein changes in mice with diabetes induced by multiple-low doses of streptozotocin: An experimental study. IJRM. 2018; 16 (4) :235-246
URL: http://journals.ssu.ac.ir/ijrmnew/article-1-1060-en.html
1- Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
2- School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand
3- Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand , sittia@kku.ac.th
Abstract:   (1523 Views)
Background: The streptozotocin (STZ)-induced diabetic model is widely used to evaluate the adverse effects of diabetes mellitus (DM) on spermatogenesis and testicular steroidogenesis. However, the actual mechanism of sub/infertility in DM males needs to be elucidated.
Objective: To conduct a detailed examination of the testicular histopathology, sperm acrosome reaction (AR) status, and tyrosine-phosphorylated protein expression in the testis of male mice induced with STZ.
Materials and Methods: Ten ICR mice were divided into two groups (n=5/each): control and diabetes induced by multiple low doses of streptozotocin (MLD-STZ). The control mice were intraperitoneally injected with citrate buffer, whereas MLD-STZ mice were injected with STZ at 40 mg/kg body weight for five consecutive days. At the end of the experiment (day 40), reproductive parameters, AR status, and the histopathology of the testis and epididymis were evaluated. The expression of testicular tyrosine phosphorylated proteins was examined.
Results: Blood glucose levels, AR percentages, and sperm abnormality of STZ group were significantly higher (p=0.003, 0.001, 0.000), while sperm concentration was significantly lower (p=0.001) compared to control. Histopathology of the seminiferous tubule was classified into 7 types. Additionally, abundant round cells were found in the epididymal lumen of the MLD-STZ mice. Moreover, the intensities of testicular phosphorylated proteins (170, 70, 36, 30, and 25 kDas) were markedly higher and a 120 kDa protein band was noticeably lower in the MLD-STZ mice.
Conclusion: MLD-STZ-induced DM causes many testicular histopathologies, precocious sperm AR, and increased expression of testicular phosphorylated proteins. These findings may clarify some mechanisms of sub/infertility in DM males.
Full-Text [PDF 937 kb]   (395 Downloads) |   |   Full-Text (HTML)  (440 Views)  
Type of Study: Original Article | Subject: Reproductive Biology

1. Bhattacharya SM, Ghosh M, Nandi N. Diabetes mellitus and abnormalities in semen analysis. J Obstet Gynaecol Res 2014; 40: 167-171. [DOI:10.1111/jog.12149]
2. Ballester J, Munoz MC, Dominguez J, Rigau T, Guinovart JJ, Rodriguez-Gil JE. Insulin-dependent diabetes affects testicular function by FSH- and LH-linked mechanisms. J Androl 2004; 25: 706-719. [DOI:10.1002/j.1939-4640.2004.tb02845.x]
3. Fernandes GS, Fernandez CD, Campos KE, Damasceno DC, Anselmo-Franci JA, Kempinas WD. Vitamin C partially attenuates male reproductive deficits in hyperglycemic rats. Reprod Biol Endocrinol 2011; 9: 100. [DOI:10.1186/1477-7827-9-100]
4. Yanagimachi R. Mammalian fertilization. The physiology of reproduction. Raven Press, New York; 1994.
5. Hunter T, Cooper JA. Protein tyrosine kinases. Annu Rev Biochem 1985; 54: 897-930. [DOI:10.1146/annurev.bi.54.070185.004341]
6. Iamsaard S, Burawat J, Kanla P, Arun S, Sukhorum W, Sripanidkulchai B, et al. Antioxidant activity and protective effect of Clitoria ternatea flower extract on testicular damage induced by ketoconazole in rats. J Zhejiang Univ Sci B 2014; 15: 548-555. [DOI:10.1631/jzus.B1300299]
7. Arad-Dann H, Beller U, Haimovitch R, Gavrieli Y, Ben-Sasson SA. Immuno-histochemistry of phosphotyrosine residues: identification of distinct intracellular patterns in epithelial and steroidogenic tissues. J Histochem Cytochem 1993; 41: 513-519. [DOI:10.1177/41.4.7680679]
8. Salicioni AM, Platt MD, Wertheimer EV, Arcelay E, Allaire A, Sosnik J, et al. Signalling pathways involved in sperm capacitation. Soc Reprod Fertil Suppl 2007; 65: 245-59.
9. Shivaji S, Kumar V, Mitra K, Jha KN. Mammalian sperm capacitation: role of phosphotyrosine proteins. Soc Reprod Fertil Suppl 2007; 63: 295-312.
10. Stival C, Puga Molina Ldel C, Paudel B, Buffone MG, Visconti PE, Krapf D. Sperm capacitation and acrosome reaction in mammalian sperm. Adv Anat Embryol Cell Biol 2016; 220: 93-106. [DOI:10.1007/978-3-319-30567-7_5]
11. Arun S, Burawat, J, Sukhorum W, Sampannang A, Maneenin C, Iamsaard S. Chronic restraint stress induces sperm acrosome reaction and changes in testicular tyrosine phosphorylated proteins in rats. Int J Reprod Biomed 2016; 14: 443-452. [DOI:10.29252/ijrm.14.7.2]
12. Arun S, Burawat J, Sukhorum W, Sampannang A, Uabundit N, Iamsaard S. Changes of testicular phosphorylated proteins in response to restraint stress in male rats. J Zhejiang Univ Sci B 2016; 17: 21-29. [DOI:10.1631/jzus.B1500174]
13. Sampannang A, Arun S, Sukhorum W, Burawat J. Nualkaew S, Maneenin C, et al. Antioxidant and hypoglycemic effects of Momordica cochinchinensis Spreng (Gac) aril extract on reproductive damages in streptozotocin (STZ)-induced hyperglycemia mice. Int J Morphol 2017; 35: 667-675. [DOI:10.4067/S0717-95022017000200046]
14. Sukhorum W, Iamsaard S. Changes in testicular function proteins and sperm acrosome status in rats treated with valproic acid. Reprod Fertil Dev 2017; 29: 1585-1592. [DOI:10.1071/RD16205]
15. Ward MA. Intracytoplasmic sperm injection effects in infertile azh mutant mice. Biol Reprod 2005; 73: 193-200. [DOI:10.1095/biolreprod.105.040675]
16. Navarro-Casado L, Juncos-Tobarra MA, Cháfer-Rudilla M, de Onzo-o LÍ, Blázquez-Cabrera JA, Miralles-García JM. Effect of experimental diabetes and STZ on male fertility capacity. Study in rats. J Androl 2010; 31: 584-592. [DOI:10.2164/jandrol.108.007260]
17. Ventura-Sobrevilla J, Boone-Villa VD, Aguilar CN, Román-Ramos R, Vega-Avila E, Campos-Sepúlveda E, et al. Effect of varying dose and administration of streptozotocin on blood sugar in male CD1 mice. Proc West Pharmacol Soc 2011; 54: 5-9.
18. Alves MG, Martins AD, Rato L, Moreira PI, Socorro S, Oliveira PF. Molecular mechanisms beyond glucose transport in diabetes-related male infertility. Biochim Biophys Acta 2013; 1832: 626-635. [DOI:10.1016/j.bbadis.2013.01.011]
19. Ahmadi A, Fajri M, Sadrkhanlou RA, Mokhtari M. Evaluation of epididymal sperm quality, DNA damage and sperm maturation abnormality in streptozotocin- induced diabetic mice. Int J Fertil Steril 2011; 5: 40.
20. Akinola OB, Biliaminu SA, Adedeji OG, Oluwaseun BS, Olawoyin OM, Adelabu TA. Combined effects of chronic hyperglycaemia and oral aluminium intoxication on testicular tissue and some male reproductive parameters in Wistar rats. Andrologia 2015; 48: 779-786. [DOI:10.1111/and.12512]
21. Xu Y, Lei H, Guan R, Gao Z, Li H, Wang L, et al. Studies on the mechanism of testicular dysfunction in the early stage of a streptozotocin induced diabetic rat model. Biochem Biophys Res Commun 2014; 450: 87-92. [DOI:10.1016/j.bbrc.2014.05.067]
22. Kianifard D, Sadrkhanlou RA, Hasanzadeh S. The ultrastructural changes of the sertoli and leydig cells following streptozotocin induced diabetes. Iran J Basic Med Sci 2012; 15: 623-635.
23. Murray FT, Orth J, Gunsalus G, Weisz J, Li JB, Jefferson LS, et al. The pituitary-testicular axis in the streptozotocin diabetic male rat: evidence for gonadotroph, Sertoli cell and Leydig cell dysfunction. Int J Androl 1981; 4: 265-280. [DOI:10.1111/j.1365-2605.1981.tb00710.x]
24. Vares G, Wang B, Ishii-Ohba H, Nenoi M, Nakajima T. Diet-induced obesity modulates epigenetic responses to ionizing radiation in mice. PLoS One 2014; e106277. [DOI:10.1371/journal.pone.0106277]
25. Ogawa T, Ito C, Nakamura T, Tamura Y, Yamamoto T, Noda T, et al. Abnormal sperm morphology caused by defects in Sertoli cells of Cnot7 knockout mice. Arch Histol Cytol 2004; 67: 307-314. [DOI:10.1679/aohc.67.307]
26. Nakamura T, Yao R, Ogawa T, Suzuki T, Ito C, Tsunekawa N, et al. Oligo-astheno- teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta. Nat Genet 2004; 36: 528-533. [DOI:10.1038/ng1344]
27. Cheon YP, Cho HJ, Kim KS. Spermatozoa characteristics of streptozotocin-induced diabetic Zucker lean rat: calcium ionophore-induced acrosome reaction and sperm concentration. Korean J Lab Anim Sci 1998, 14, 15-20.
28. Cheon YP, Kim CH, Kang BM, Chang YS, Nam JH, Kim YS, et al. Spermatozoa characteristics of streptozotocin-induced diabetic Wistar rat: acrosome reaction and spermatozoa concentration. Korean J Fertil Steril 1999; 26: 89-96.
29. Ayer-LeLievre C, Olson L, Ebendal T, Hallbook F, Persson H. Nerve growth factor mRNA and protein in the testis and epididymis of mouse and rat. Proc Nat Acad Sci USA 1988; 85: 2628-2632. [DOI:10.1073/pnas.85.8.2628]
30. Sisman AR, Kiray M, Camsari UM, Evren M, Ates M, Baykara B, et al. Potential novel biomarkers for diabetic testicular damage in streptozotocin-induced diabetic rats: nerve growth factor beta and vascular endothelial growth factor. Dis Markers 2014; 2014: 108106-108112. [DOI:10.1155/2014/108106]
31. Jin W, Tanaka A, Watanabe G, Matsuda H, Taya K. Effect of NGF on the motility and acrosome reaction of golden hamster spermatozoa in vitro. J Reprod Dev 2010; 56: 437-443. [DOI:10.1262/jrd.09-219N]
32. Donmez YB, Kizilay G, Topcu-Tarladacalisir Y. MAPK immunoreactivity in streptozotocin- induced diabetic rat testis. Acta Cir Bras 2014; 29: 644-650. [DOI:10.1590/S0102-8650201400160004]
33. Adewole SO, Caxton-Martins EA, Salako AA, Doherty OW, Naicker T. Effects of oxidative stress induced by streptozotocin on the morphology and trace minerals of the testes of diabetic wistar rats. Pharmacologyonline 2007; 2: 478-497.
34. Amaral S, Mota PC, Lacerda B, Alves M, Pereira Mde L, Oliveira PJ, et al. Testicular mitochondrial alterations in untreated streptozotocin-induced diabetic rats. Mitochondrion 2009; 9: 41-50. [DOI:10.1016/j.mito.2008.11.005]
35. Creasy DM. Pathogenesis of Male Reproductive Toxicity. Toxicol Pathol 2001; 29: 64-76. [DOI:10.1080/019262301301418865]
36. Khaneshi F, Nasrolahi O, Azizi S, Nejati V. Sesame effects on testicular damage in streptozotocin-induced diabetes rats. Avicenna J Phytomed 2013; 3: 347-355.
37. Shi Q, King RW. Chromosome nondisjunction yields tetraploid rather than aneuploid cells in human cell lines. Nature 2005; 437: 1038-1042. [DOI:10.1038/nature03958]
38. Vidal JD, Whitney KM. Morphologic manifestations of testicular and epididymal toxicity. Spermatogenesis 2014; 4: e979099. [DOI:10.4161/21565562.2014.979099]
39. Tsounapi P, Honda M, Dimitriadis F, Kawamoto B, Hikita K, Muraoka K, et al. Impact of antioxidants on seminal vesicles function and fertilizing potential in diabetic rats. Asian J Androl 2016; 19: 639-646.

Send email to the article author

© 2021 All Rights Reserved | International Journal of Reproductive BioMedicine

Designed & Developed by : Yektaweb