Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility

Asian Journal of Andrology

Volumn 18, Issue 2, 2016, Pages 282-291

  Agarwal, Ashok ^a   Sharma, Rakesh ^a   Samanta, Luna ^b   Durairajanayagam, Damayanthi ^a,c   Sabanegh, Edmund ^a  

^a LERNER RESEARCH INSTITUTE   (United States)

^b RAVENSHAW UNIVERSITY   (India)

^c MARA University of Technology (UiTM)   (Malaysia)

Author keywords

bioinformatics; male infertility; proteomics; spermatozoa proteins; varicocele

Indexed keywords

CHAPERONE; PROTEIN AK7; PROTEIN CCT6B; PROTEIN DERIVATIVE; PROTEIN HSPA2; PROTEIN ODF2; PROTEIN PKAR1A; UNCLASSIFIED DRUG; BIOLOGICAL MARKER; REACTIVE OXYGEN METABOLITE;

ARTICLE; CITRIC ACID CYCLE; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOWN REGULATION; HUMAN; HUMAN CELL; HYPERTHERMIA; HYPOXIA; LIPID METABOLISM; MALE; MALE INFERTILITY; PROTEOMICS; RESPIRATORY CHAIN; SPERMATOGENESIS; SPERMATOZOON MOTILITY; VALIDATION STUDY; VARICOCELE; WESTERN BLOTTING; CASE CONTROL STUDY; CHEMISTRY; COMPLICATION; DNA FRAGMENTATION; GENE EXPRESSION PROFILING; INFERTILITY, MALE; METABOLISM; MITOCHONDRIAL DISEASES; PHYSIOLOGY; SPERMATOZOON;

BIOMARKERS; BLOTTING, WESTERN; CASE-CONTROL STUDIES; DNA FRAGMENTATION; GENE EXPRESSION PROFILING; HUMANS; INFERTILITY, MALE; MALE; MITOCHONDRIAL DISEASES; PROTEOMICS; REACTIVE OXYGEN SPECIES; SPERM MOTILITY; SPERMATOGENESIS; SPERMATOZOA; VARICOCELE;

EID: 84957876654     PISSN: 1008682X     EISSN: 17457262     Source Type: Journal    
DOI: 10.4103/1008-682X.170445     Document Type: Article

References (80)

1. Baazeem A, Belzile E, Ciampi A, Dohle G, Jarvi K, et al. Varicocele, and male factor infertility treatment: a new meta-Analysis, and review of the role of varicocele repair. Eur Urol. 2011; 60: 796-808.
2. Practice Committee of American Society for Reproductive Medicine. Report on varicocele, and infertility. Fertil Steril. 2008; 90: S247-9.
3. Agarwal A, Prabakaran S, Allamaneni SS. Relationship between oxidative stress, varicocele, and infertility: a meta-Analysis. Reprod Biomed Online. 2006; 12: 630-3.
4. Sheehan MM, Ramasamy R, Lamb DJ. Molecular mechanisms involved in varicocele-Associated infertility. J Assist Reprod Genet. 2014; 31: 521-6.
5. Cocuzza M, Cocuzza MA, Bragais FM, Agarwal A. The role of varicocele repair in the new era of assisted reproductive technology. Clinics. 2008; 63: 395-404.
6. Marmar JL. The pathophysiology of varicoceles in the light of current molecular, and genetic information. Hum Reprod Update. 2001; 7: 461-72.
7. Bertolla RP, Cedenho AP, Hassun Filho PA, Lima SB, Ortiz V, et al. Sperm nuclear DNA fragmentation in adolescents with varicocele. Fertil Steril. 2006; 85: 625-8.
8. Blumer CG, Fariello RM, Restelli AE, Spaine DM, Bertolla RP, et al. Sperm nuclear DNA fragmentation, and mitochondrial activity in men with varicocele. Fertil Steril. 2008; 90: 1716-22.
9. Zini A, Dohle G. Are varicoceles associated with increased deoxyribonucleic acid fragmentation?. Fertil Steril. 2011; 96: 1283-7.
10. Libman J, Jarvi K, Lo K, Zini A. Beneficial effect of microsurgical varicocelectomy is superior for men with bilateral versus unilateral repair. J Urol. 2006; 176: 2602-5.
11. Hamada A, Sharma R, du Plessis SS, Willard B, Yadav SP, et al. Two-dimensional differential in-gel electrophoresis-based proteomics of male gametes in relation to oxidative stress. Fertil Steril. 2013; 99: 1216-26.
12. Sharma R, Agarwal A, Mohanty G, Du Plessis SS, Gopalan B, et al. Proteomic analysis of seminal fluid from men exhibiting oxidative stress. Reprod Biol Endocrinol 2013a; 11: 85.
13. Sharma R, Agarwal A, Mohanty G, Hamada AJ, Gopalan B, et al. Proteomic analysis of human spermatozoa proteins with oxidative stress. Reprod Biol Endocrinol. 2013; 11: 8.
14. Amaral A, Paiva C, Attardo Parrinello C, Estanyol JM, Ballesca JL, et al. Identification of proteins involved in human sperm motility using high-Throughput differential proteomics. J Proteome Res. 2014; 13: 5670-84.
15. Legare C, Droit A, Fournier F, Bourassa S, Force A, et al. Investigation of male infertility using quantitative comparative proteomics. J Proteome Res. 2014; 13: 5403-14.
16. Hosseinifar H, Gourabi H, Salekdeh GH, Alikhani M, Mirshahvaladi S, et al. Study of sperm protein profile in men with, and without varicocele using two-dimensional gel electrophoresis. Urology. 2013; 81: 293-300.
17. Chan CC, Sun GH, Shui HA, Wu GJ. Differential spermatozoal protein expression profiles in men with varicocele compared to control subjects: upregulation of heat shock proteins 70, and 90 in varicocele. Urology. 2013; 81: 1379.e1-8.
18. Ferlin A, Speltra E, Patassini C, Pati MA, Garolla A, et al. Heat shock protein, and heat shock factor expression in sperm: relation to oligozoospermia, and varicocele. J Urol. 2010; 183: 1248-52.
19. Camargo M, Intasqui Lopes P, Del Giudice PT, Carvalho VM, Cardozo KH, et al. Unbiased label-free quantitative proteomic profiling, and enriched proteomic pathways in seminal plasma of adult men before, and after varicocelectomy. Hum Reprod. 2013; 28: 33-46.
20. Hosseinifar H, Sabbaghian M, Nasrabadi D, Modarresi T, Dizaj AV, et al. Study of the effect of varicocelectomy on sperm proteins expression in patients with varicocele, and poor sperm quality by using two-dimensional gel electrophoresis. J Assist Reprod Genet. 2014; 31: 725-9.
21. Agarwal A, Sharma R, Durairajanayagam D, Ayaz A, Cui Z, et al. Major protein alterations in spermatozoa from infertile men with unilateral varicocele. Reprod Biol Endocrinol. 2015; 13: 7.
22. Agarwal A, Sharma R, Durairajanayagam D, Cui Z, Ayaz A, et al. Spermatozoa protein alterations in infertile men with bilateral varicocele. Asian J Androl. 2015; May 22. doi: 10.4103/1008-682X.153848. [Epub ahead of print].
23. Agarwal A, Sharma R, Durairajanayagam D, Cui Z, Ayaz A, et al. Differential proteomic profiling of spermatozoal proteins of infertile men with unilateral or bilateral varicocele. Urology. 2015; 85: 580-3.
24. WHO. World Health Organization Laboratory Manual for the Examination, and Processing of Human Semen. 5th ed. Switzerland, Geneva: World Health Organization Press; 2010.
25. Kashou AH, Sharma R, Agarwal A. Assessment of oxidative stress in sperm, and semen. Methods Mol Biol. 2013; 927: 351-61.
26. Sharma RK, Sabanegh E, Mahfouz R, Gupta S, Thiyagarajan A, et al. TUNEL as a test for sperm DNA damage in the evaluation of male infertility. Urology. 2010; 76: 1380-6.
27. Keller A, Nesvizhskii AI, Kolker E, Aebersold R. Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS, and database search. Anal Chem. 2002; 74: 5383-92.
28. Nesvizhskii AI, Keller A, Kolker E, Aebersold R. A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem. 2003; 75: 4646-58.
29. Ashburner M. A biologist's view of the Drosophila genome annotation assessment project. Genome Res. 2000; 10: 391-3.
30. Zhang Y, Wen Z, Washburn MP, Florens L. Refinements to label free proteome quantitation. How to deal with peptides shared by multiple proteins. Anal Chem. 2010; 82: 2272-81.
31. Zybailov B, Coleman MK, Florens L, Washburn MP. Correlation of relative abundance ratios derived from peptide ion chromatograms, and spectrum counting for quantitative proteomic analysis using stable isotope labeling. Anal Chem. 2005; 77: 6218-24.
32. Boyle EI, Weng S, Gollub J, Jin H, Botstein D, et al. GO: TermFinder-open source software for accessing Gene Ontology information, and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics. 2004; 20: 3710-5.
33. Bhatia VN, Perlman DH, Costello CE, McComb ME. Software tool for researching annotations of proteins: open-source protein annotation software with data visualization. Anal Chem. 2009; 81: 9819-23.
34. Naaby-Hansen S, Flickinger CJ, Herr JC. Two-dimensional gel electrophoretic analysis of vectorially labelled surface proteins of human spermatozoa. Biol Reprod. 1997; 56: 771-87.
35. Baker MA, Reeves G, Hetherington L, Muller J, Baur I, et al. Identification of gene products present in Triton X-100 soluble, and insoluble fractions of human spermatozoa lysates using LC-MS/MS analysis. Proteomics Clin Appl. 2007; 1: 524-32.
36. Brewis IA, Gadella BM. Sperm surface proteomics: from protein lists to biological function. Mol Hum Reprod. 2010; 16: 68-79.
37. Lima SB, Cenedeze MA, Bertolla RP, Filho PA, Oehninger S, et al. Expression of the HSPA2 gene in ejaculated spermatozoa from adolescents with, and without varicocele. Fertil Steril. 2006; 86: 1659-63.
38. Yesilli C, Mungan G, Seckiner I, Akduman B, Acikgoz S, et al. Effect of varicocelectomy on sperm creatine kinase, HspA2 chaperone protein (creatine kinase-M type), LDH, LDH-X, and lipid peroxidation product levels in infertile men with varicocele. Urology. 2005; 66: 610-5.
39. Siva AB, Kameshwari DB, Singh V, Pavani K, Sundaram CS, et al. Proteomics-based study on asthenozoospermia: differential expression of proteasome alpha complex. Mol Hum Reprod. 2010; 16: 452-62.
40. Preissner KT, Bronson RA. The role of multifunctional adhesion molecules in spermatogenesis, and sperm function: lessons from hemostasis, and defense?. Semin Thromb Hemost. 2007; 33: 100-10.
41. D'Cruz OJ, Haas GG Jr. Beta 2-integrin (CD11b/CD18) is the primary adhesive glycoprotein complex involved in neutrophil-mediated immune injury to human sperm. Biol Reprod. 1995; 53: 1118-30.
42. Hu T, Guan T, Gerace L. Molecular, and functional characterization of the p62 complex, an assembly of nuclearporecomplex glycoproteins. J Cell Biol. 1996; 134: 589-601.
43. Shum WW, Da Silva N, Brown D, Breton S. Regulation of luminal acidification in the male reproductive tract via cell-cell crosstalk. J Exp Biol. 2009; 212: 1753-61.
44. Sun-Wada GH, Imai-Senga Y, Yamamoto A, Murata Y, Hirata T, et al. A proton pump ATPase with testis-specific E1-subunit isoform required for acrosome acidification. J Biol Chem. 2002; 277: 18098-105.
45. Lleres D, Denegri M, Biggiogera M, Ajuh P, Lamond AI. Direct interaction between hnRNP-M, and CDC5L/PLRG1 proteins affects alternative splice site choice. EMBO Rep. 2010; 11: 445-51.
46. Hovhannisyan RH, Carstens RP. Heterogeneous ribonucleoprotein m is a splicing regulatory protein that can enhance or silence splicing of alternatively spliced exons. J Biol Chem. 2007; 282: 36265-74.
47. Tomes CN, De Blas GA, Michaut MA, Farre EV, Cherhitin O, et al. alpha-SNAP, and NSF are required in a priming step during the human sperm acrosome reaction. Mol Hum Reprod. 2005; 11: 43-51.
48. Michaut M, Tomes CN, De Blas G, Yunes R, Mayorga LS. Calcium-Triggered acrosomal exocytosis in human spermatozoa requires the coordinated activation of Rab3A, and N-ethylmaleimide-sensitive factor. Proc Natl Acad Sci USA. 2000; 97: 9996-10001.
49. Roggero CM, De Blas GA, Da H, Tomes CN, Rizo J, et al. Complexin/synaptotagmin interplay controls acrosomal exocytosis. J Biol Chem. 2007; 282: 26335-43.
50. Yunes R, Michaut M, Tomes C, Mayorga LS. Rab3A triggers the acrosome reaction in permeabilized human spermatozoa. Biol Reprod. 2000; 62: 1084-9.
51. Baba T, Niida Y, Michikawa Y, Kashiwabara S, Kodaira K, et al. An acrosomal protein, sp32, in mammalian sperm is a binding protein specific for two proacrosins, and an acrosin intermediate. J Biol Chem. 1994; 269: 10133-40.
52. Tardif S, Guyonnet B, Cormier N, Cornwall GA. Alteration in the processing of the ACRBP/sp32 protein, and sperm head/acrosome malformations in proprotein convertase 4 (PCSK4) null mice. Mol Hum Reprod. 2012; 18: 298-307.
53. Naughton CK, Nangia AK, Agarwal A. Pathophysiology of varicoceles in male infertility. Hum Reprod Update. 2001; 7: 473-81.
54. Guzy RD, Schumacker PT. Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia. Exp Physiol. 2006; 91: 807-19.
55. Paul C, Teng S, Saunders PT. A single, mild, transient scrotal heat stress causes hypoxia, and oxidative stress in mouse testes, which induces germ cell death. Biol Reprod. 2009; 80: 913-9.
56. Vivas-Acevedo G, Lozano-Hernandez R, Camejo MI. Markers of accessory sex glands function in men with varicocele, relationship with seminal parameters. Can J Urol. 2011; 18: 5884-9.
57. Vivas-Acevedo G, Lozano-Hernandez R, Camejo MI. Varicocele decreases epididymal neutral ?-glucosidase, and is associated with alteration of nuclear DNA, and plasma membrane in spermatozoa. BJU Int. 2014; 113: 642-9.
58. Roaiah MM, Mostafa T, Salem D, El-Nashar AR, Kamel II, et al. Alpha-1, 4-Glucosidase activity in infertile oligoasthenozoospermic men with, and without varicocele. Andrologia. 2007; 39: 28-32.
59. Rodova M, Nguyen AN, Blanco G. The transcription factor CREMtau, and cAMP regulate promoter activity of the Na, K-ATPase alpha4 isoform. Mol Reprod Dev. 2006; 73: 1435-47.
60. Lindquist S, Craig EA. The heat-shock proteins. Annu Rev Genet. 1988; 22: 631-77.
61. Naaby-Hansen S, Herr JC. Heat shock proteins on the human sperm surface. J Rep Immunol. 2010; 84: 32-40.
62. Bukau B, Weissman J, Horwich A. Molecular chaperones, and protein quality control. Cell. 2006; 125: 443-51.
63. Ayaz A, Agarwal A, Sharma R, Arafa M, Elbardisi H, et al. Impact of precise modulation of reactive oxygen species levels on spermatozoa proteins in infertile men. Clin Proteomics. 2015; 12: 4.
64. Kubota H, Hynes GM, Kerr SM, Willison KR. Tissue-specific subunit of the mouse cytosolic chaperonin-containing TCP-1. FEBS Lett. 1997; 402: 53-6.
65. Pixton KL, Deeks ED, Flesch FM, Moseley FL, Bjorndahl L, et al. Sperm proteome mapping of a patient who experienced failed fertilization at IVF reveals altered expression of at least 20 proteins compared with fertile donors: case report. Hum Reprod. 2004; 19: 1438-47.
66. Zhao C, Huo R, Wang FQ, Lin M, Zhou ZM, et al. Identification of several proteins involved in regulation of sperm motility by proteomic analysis. Fertil Steril. 2007; 87: 436-8.
67. Panayiotou C, Solaroli N, Xu Y, Johansson M, Karlsson A. The characterization of human adenylate kinases 7, and 8 demonstrates differences in kinetic parameters, and structural organization among the family of adenylate kinase isoenzymes. Biochem J. 2011; 433: 527-34.
68. Chiriva-Internati M, Gagliano N, Donetti E, Costa F, Grizzi F, et al. Sperm protein 17 is expressed in the sperm fibrous sheath. J Transl Med. 2009; 7: 61.
69. Askautrud HA, Gjernes E, Gunnes G, Sletten M, Ross DT, et al. Global gene expression analysis reveals a link between NDRG1, and vesicle transport. PLoS One. 2014; 9: e87268.
70. Brosens JJ, Hodgetts A, Feroze-Zaidi F, Sherwin JR, Fusi L, et al. Proteomic analysis of endometrium from fertile, and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure, and endometriosis. Mol Hum Reprod. 2010; 16: 273-85.
71. Lee YH, Choi SH, Lee KW, Kim DJ. Apolipoprotein B/A1 ratio is associated with free androgen index, and visceral adiposity, and may be an indicator of metabolic syndrome in male children, and adolescents. Clin Endocrinol (Oxf) 2011; 74: 579-86.
72. Romeo C, Ientile R, Impellizzeri P, Turiaco N, Teletta M, et al. Preliminary report on nitric oxide-mediated oxidative damage in adolescent varicocele. Hum Reprod. 2003; 18: 26-9.
73. Munier A, Feral C, Milon L, Pinon VP, Gyapay G, et al. A new human nm23 homologue (nm23-H5) specifically expressed in testis germinal cells. FEBS lett. 1998; 434: 289-94.
74. Burton KA, McDermott DA, Wilkes D, Poulsen MN, Nolan MA, et al. Haploinsufficiency at the protein kinase A RI alpha gene locus leads to fertility defects in male mice, and men. Mol Endocrinol. 2006; 20: 2504-13.
75. Makino Y, Kanemaki M, Kurokawa Y, Koji T, Tamura TA. A rat RuvB-like protein, TIP49a, is a germ cell-enriched novel DNA helicase. J Biol Chem. 1999; 274: 15329-35.
76. Ikeda S, Yamaoka-Tojo M, Hilenski L, Patrushev NA, Anwar GM, et al. IQGAP1 regulates reactive oxygen species-dependent endothelial cell migration through interacting with Nox2. Arterioscler Thromb Vasc Biol. 2005; 25: 2295-300.
77. Diekman AB, Norton EJ, Klotz KL, Westbrook VA, Shibahara H, et al. N-linked glycan of a sperm CD52 glycoform associated with human infertility. FASEB J. 1999; 13: 1303-13.
78. Li Y, Roux C, Lazereg S, LeCaer JP, Laprevote O, et al. Identification of a novel serine phosphorylation site in human glutamine: fructose-6-phosphateamidotransferase isoform 1. Biochemistry. 2007; 46: 13163-9.
79. Zhang X, Fang J, Xu B, Zhang S, Su S, et al. correlation of epididymal protease inhibitor, and fibronectin in human semen. PLoS One. 2013; 8: e82600.
80. Diaz ES, Kong M, Morales P. Effect of fibronectin on proteasome activity, acrosome reaction, tyrosine phosphorylation, and intracellular calcium concentrations of human sperm. Hum Reprod. 2007; 22: 1420-30.