Volume 12, Issue 5 (6-2014)                   IJRM 2014, 12(5): 313-0 | Back to browse issues page

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Nazarian H, Ghaffari Novin M, Jalili M R, Mirfakhraie R, Heidari M H, Hosseini S J, et al . Expression of Glycogen synthase kinase 3-β (GSK3-β) gene in azoospermic men. IJRM 2014; 12 (5) :313-0
URL: http://ijrm.ir/article-1-544-en.html
Expression of Glycogen synthase kinase 3-β (GSK3-β) gene in azoospermic men
Hamid Nazarian1 , Marefat Ghaffari Novin * 2, Mohammad Reza Jalili1 , Reza Mirfakhraie3 , Mohammad Hassan Heidari1 , Seyed Jalil Hosseini1 , Mohsen Norouzian1 , Nahid Ehsani4
1- Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2- Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran , mghaffarin@yahoo.com
3- Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4- Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract:   (2810 Views)
Background: The Wnt/β- The Wnt/β-catenin signaling pathway is involved in many developmental processes in both fetal and adult life; its abnormalities can lead to disorders including several types of cancers and malfunction of specific cells and tissues in both animals and humans. Its role in reproductive processes has been proven.
Objective: This study was designed to evaluate the expression of the key regulator of this signaling pathway GSK3-β and its presumed role in azoospermia.
Materials and Methods: WNT3a protein concentration and GSK3-β gene expression levels were measured and compared between two groups of infertile men. The test groups consisted of 10 patients with obstructive and 10 non-obstructive azoospermia. The control group was selected among healthy men after vasectomies that were willing to conceive a child using a testicular biopsy technique. Samples were obtained by testicular biopsy and screened for the most common mutations (84, 86 and 255) in the SRY region before analyzing. GSK3-β gene expression was assessed quantitatively by real time-PCR.
Results: The WNT3a protein concentration had no significant difference between the two test groups and controls. Expression of GSK3-β was down-regulated in non-obstructive azoospermia (3.10±0.19) compared with normal (7.12±0.39) and obstructive azoospermia (6.32±0.42) groups (p=0.001).
Conclusion: Down-regulation of GSK-3β may cause to non-obstructive azoospermia. Regulation and modification of GSK-3β gene expression by drugs could be used as a therapeutic solution.
Keywords: Azoospermia, Wnt signaling pathway, glycogen synthase kinase 3 beta, Spermatogenesis.
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Type of Study: Original Article |
References
1. De Kretser DM, Baker HW. Infertility in men: recent advances and continuing controversies. J Clin Endocrinol Metab 1999; 84: 3443-3450. [DOI:10.1210/jc.84.10.3443]
2. World Health Organization. WHO laboratory manual for the examination and processing of human semen. Geneva, World Health Organization, 2010.
3. Lombardi AP, Royer C, Pisolato R, Cavalcanti FN, Lucas TF, Lazari MF, et al. Physiopathological aspects of the Wnt/beta-catenin signaling pathway in the male reproductive system. Spermatogenesis 2013; 3: e23181. [DOI:10.4161/spmg.23181]
4. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell 2012; 149: 1192-1205. [DOI:10.1016/j.cell.2012.05.012]
5. Veeman MT, Axelrod JD, Moon RT. A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell 2003; 5: 367-377. [DOI:10.1016/S1534-5807(03)00266-1]
6. Topol L, Jiang X, Choi H, Garrett-Beal L, Carolan PJ, Yang Y. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol 2003; 162: 899-908. [DOI:10.1083/jcb.200303158]
7. Mulholland DJ, Dedhar S, Coetzee GA, Nelson CC. Interaction of Nuclear Receptors with the Wnt/β-Catenin/Tcf Signaling Axis: Wnt You Like to Know? Endocr Rev 2005; 26: 898-915. [DOI:10.1210/er.2003-0034]
8. Terry S, Yang X, Chen MW, Vacherot F, Buttyan R. Multifaceted interaction between the androgen and Wnt signaling pathways and the implication for prostate cancer. J Cell Biochem 2006; 99: 402-410. [DOI:10.1002/jcb.20983]
9. Golestaneh N, Beauchamp E, Fallen S, Kokkinaki M, Uren A, Dym M. Wnt signaling promotes proliferation and stemness regulation of spermatogonial stem/progenitor cells. Reproduction 2009; 138: 1551-1562. [DOI:10.1530/REP-08-0510]
10. Tanwar PS, Kaneko-Tarui T, Zhang L, Rani P, Taketo MM, Teixeira J. Constitutive WNT/beta-catenin signaling in murine Sertoli cells disrupts their differentiation and ability to support spermatogenesis. Biol Reprod 2010; 82: 422-432. [DOI:10.1095/biolreprod.109.079335]
11. Erickson RP, Lai L-W, Grimes J. Creating a conditional mutation of Wnt-1 by antisense transgenesis provides evidence that Wnt-1 is not essential for spermatogenesis. Dev Genet 1993; 14: 274-281. [DOI:10.1002/dvg.1020140405]
12. Jeays-Ward K, Dandonneau M, Swain A. Wnt4 is required for proper male as well as female sexual development. Dev Biol 2004; 276: 431-440. [DOI:10.1016/j.ydbio.2004.08.049]
13. Katoh M. Molecular cloning and characterization of human WNT3. Int J Oncol 2001; 19: 977-982. [DOI:10.3892/ijo.19.5.977]
14. Yeh JR, Zhang X, Nagano MC. Wnt5a is a cell-extrinsic factor that supports self-renewal of mouse spermatogonial stem cells. J Cell Sci 2011; 124: 2357-2366. [DOI:10.1242/jcs.080903]
15. Ikegawa S, Kumano Y, Okui K, Fujiwara T, Takahashi E, Nakamura Y. Isolation, characterization and chromosomal assignment of the human WNT7A gene. Cytogen Cell Genet 1996; 74: 149-152. [DOI:10.1159/000134404]
16. Wang YK, Sporle R, Paperna T, Schughart K, Francke U. Characterization and expression pattern of the frizzled gene Fzd9, the mouse homolog of FZD9 which is deleted in Williams-Beuren syndrome. Genomics 1999; 57: 235-248. [DOI:10.1006/geno.1999.5773]
17. Simoni M, Bakker E, Krausz C. EAA/EMQN best practice guidelines for molecular diagnosis of y-chromosomal microdeletions. State of the art 2004. Int J Androl 2004; 27: 240-249. [DOI:10.1111/j.1365-2605.2004.00495.x]
18. Maurer B, Simoni M. Y chromosome microdeletion screening in infertile men. J Endocrinol Invest 2000; 23: 664-670. [DOI:10.1007/BF03343791]
19. Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev 2001; 22: 226-239. [DOI:10.1210/er.22.2.226]
20. Boyer A, Paquet M, Lague MN, Hermo L, Boerboom D. Dysregulation of WNT/CTNNB1 and PI3K/AKT signaling in testicular stromal cells causes granulosa cell tumor of the testis. Carcinogenesis 2009; 30: 869-878. [DOI:10.1093/carcin/bgp051]
21. Embi N, Rylatt DB, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem 1980; 107: 519-527. [DOI:10.1111/j.1432-1033.1980.tb06059.x]
22. Frame S, Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem J 2001; 359: 1-16. [DOI:10.1042/bj3590001]
23. Chang H, Gao F, Guillou F, Taketo MM, Huff V, Behringer RR. Wt1 negatively regulates beta-catenin signaling during testis development. Development 2008; 135: 1875-1885. [DOI:10.1242/dev.018572]
24. Kobayashi A, Stewart CA, Wang Y, Fujioka K, Thomas NC, Jamin SP, et al. beta-Catenin is essential for Mullerian duct regression during male sexual differentiation. Development 2011; 138: 1967-1975. [DOI:10.1242/dev.056143]
25. Kimura T, Nakamura T, Murayama K, Umehara H, Yamano N, Watanabe S, et al. The stabilization of beta-catenin leads to impaired primordial germ cell development via aberrant cell cycle progression. Dev Biol 2006; 300: 545-553. [DOI:10.1016/j.ydbio.2006.06.038]
26. Li Y, Gao Q, Yin G, Ding X, Hao J. WNT/beta-catenin-signaling pathway stimulates the proliferation of cultured adult human Sertoli cells via upregulation of C-myc expression. Reprod Sci 2012; 19: 1232-1240. [DOI:10.1177/1933719112447126]
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