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Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation

  • Gamete Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Sperm DNA fragmentation has been suggested as a marker for infertility diagnosis and prognosis. Hence, understanding its impact on male physiology and post-genomic pathways would be clinically important. We performed the proteomics and functional enrichment analyses of viable spermatozoa from ejaculates with low and high sperm DNA fragmentation to identify protein expression and pathways altered in association with sperm DNA fragmentation.

Methods

Sperm DNA fragmentation using the Comet assay and the Komet 6.0.1 software was assessed in raw samples from 89 subjects from a human reproduction service. The Low and High sperm DNA fragmentation groups were formed according to the Olive Tail Moment variable. Spermatozoa proteins from these groups were pooled and analyzed by a shotgun proteomic approach (2D nanoUPLC-ESI-MSE). Differentially expressed proteins were used for a functional enrichment study.

Results

Two hundred and fifty-seven proteins were identified or quantified in sperm from the Low and High sperm DNA fragmentation groups. Of these, seventy-one proteins were exclusively or overexpressed in the Low group, whereas twenty-three proteins were exclusively or overexpressed in the High group. One hundred and sixty-three proteins were conserved between these groups. We also functionally related the differentially expressed proteins in viable spermatozoa from the groups. Processes such as triacylglycerol metabolism, energy production, protein folding, response to unfolded proteins, and cellular detoxification were found to be altered in these cells.

Conclusions

Sperm DNA fragmentation is associated with differential protein expression in viable spermatozoa. These proteins may potentially be used as biomarkers for sperm DNA integrity.

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References

  1. Brugh VM, Lipshultz LI. Male factor infertility: evaluation and management. Med Clin North Am. 2004;88:367–85.

    PubMed  Google Scholar 

  2. Avendaño C, Franchi A, Taylor S, Morshedi M, Bocca S, Oehninger S. Fragmentation of DNA in morphologically normal human spermatozoa. Fertil Steril. 2009;91(4):1077–84.

    PubMed  Google Scholar 

  3. Saleh RA, Agarwal A, Nada EA, EI-Tonsy MH, Sharma RK, Meyer A, et al. Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril. 2003;79(S3):1597–605.

    PubMed  Google Scholar 

  4. Balhorn R, Cosman M, Thornton K, Krishnan VV, Corzett M, Bench G, et al. Protamine mediated condensation of DNA in mammalian sperm. In: Gagnon C, editor. The male gamete: From basic science to clinical applications. Vienna: Cache River Press; 1999. p. 55–70.

    Google Scholar 

  5. Barroso G, Morshedi M, Oehninger S. Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum Reprod. 2000;15:1338–44.

    PubMed  CAS  Google Scholar 

  6. Sakkas D, Moffatt O, Manicardi GC, Mariethoz E, Tarozzi N, Bizzaro D. Nature of DNA damage in ejaculated human spermatozoa and the possible involvement of apoptosis. Biol Reprod. 2003;66:1061–7.

    Google Scholar 

  7. Sakkas D, Mariethoz E, St John JC. Abnormal sperm parameters in humans are indicative of an abortive apoptotic mechanism linked to the Fas-mediated pathway. Exp Cell Res. 1999;251(2):350–5.

    PubMed  CAS  Google Scholar 

  8. O’Brien J, Zini A. Sperm DNA integrity and male infertility. Urology. 2005;65:16–22.

    PubMed  Google Scholar 

  9. Benchaib M, Braun V, Lornage J, Hadj S, Salle B, Lejeune H, et al. Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Hum Reprod. 2003;18(5):1023–8.

    PubMed  Google Scholar 

  10. Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, Erenpreiss J, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2007;22:174–9.

    PubMed  CAS  Google Scholar 

  11. Loft S, Kold-Jensen T, Hjollund NH, Giwercman A, Gyllemborg J, Ernst E, et al. Oxidative DNA damage in human sperm influences time to pregnancy. Hum Reprod. 2003;18:1265–72.

    PubMed  CAS  Google Scholar 

  12. Shamsi MB, Kumar R, Dada R. Evaluation of nuclear DNA damage in human spermatozoa in men opting for assisted reproduction. Indian J Med Res. 2008;127:115–23.

    PubMed  CAS  Google Scholar 

  13. Tomsu M, Sharma V, Miller D. Embryo quality and IVF treatment outcomes may correlate with different sperm comet assay parameters. Hum Reprod. 2002;17(7):1856–62.

    PubMed  CAS  Google Scholar 

  14. Borini A, Tarozzi N, Bizzaro D, Bonu MA, Fava L, Flamigni C, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006;21(11):2876–81.

    PubMed  CAS  Google Scholar 

  15. Seli E, Gardner DK, Schoolcraft WB, Moffatt O, Sakkas D. Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril. 2004;82:378–83.

    PubMed  Google Scholar 

  16. Practice Committee of American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2012;98(2):294–301.

    Google Scholar 

  17. Evenson DP, Darzynkiewicz Z, Melamed MR. Relation of mammalian sperm chromatin heterogeneity to fertility. Science. 1980;210:1131–3.

    PubMed  CAS  Google Scholar 

  18. Spano M, Bonde JP, Hjollund HI, Kolstad HA, Cordelli E, Leter G. Sperm chromatin damage impairs human fertility. Fertil Steril. 2000;73:43–50.

    PubMed  CAS  Google Scholar 

  19. Zini A, Sigman M. Are tests of sperm DNA damage clinically useful? pros and cons. J Androl. 2009;30(3):219–29.

    PubMed  CAS  Google Scholar 

  20. Huszar G, Patrizio P, Vigue L, Willets M, Wilker C, Adhoot D, et al. Cytoplasmic extrusion and the switch from creatine kinase B to M isoform are completed by the commencement of epididymal transport in human and stallion spermatozoa. J Androl. 1998;19(1):11–20.

    PubMed  CAS  Google Scholar 

  21. Sakkas D. Novel technologies for selecting the best sperm for in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2013. doi:10.1016/j.fertnstert.2012.12.025.

    Google Scholar 

  22. Sharpe RM. Regulation of Spermatogenesis. In: Knobil E, Neil JD, editors. The physiology of reproduction. 2nd ed. New York: Raven Press, Ltd.; 1994. p. 1363–434.

    Google Scholar 

  23. Shen HM, Dai J, Chia SE, Lim A, Ong CN. Detection of apoptotic alterations in sperm in subfertile patients and their correlations with sperm quality. Hum Reprod. 2002;17(5):1266–73.

    PubMed  Google Scholar 

  24. González-Marín C, Gosálvez J, Roy R. Types, causes, detection and repair of DNA fragmentation in animal and human sperm cells. Int J Mol Sci. 2012;13(11):14026–52.

    PubMed  Google Scholar 

  25. McVicar CM, McClure N, Williamson K, Dalzell LH, Lewis SE. Incidence of Fas positivity and deoxyribonucleic acid double-stranded breaks in human ejaculated sperm. Fertil Steril. 2004;81 Suppl 1:767–74.

    PubMed  CAS  Google Scholar 

  26. Dacheux JL, Voglmayr JK. Sequence of sperm cell surface differentiation and its relationship to exogenous fluid proteins in the ram epididymis. Biol Reprod. 1983;29:1033–46.

    PubMed  CAS  Google Scholar 

  27. WHO (World Health Organization). Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 5th ed. New York: Cambridge University Press; 2010.

    Google Scholar 

  28. Kruger TF, Menkveld R, Stander FS, Lombard CJ, Van der Merwe JP, van Zyl JA, et al. Sperm morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril. 1986;46:1118–23.

    PubMed  CAS  Google Scholar 

  29. Fariello RM, Del Giudice PT, Spaine DM, Fraietta R, Bertolla RP, Cedenho AP. Effect of leukocytospermia and processing by discontinuous density gradient on sperm nuclear DNA fragmentation and mitochondrial activity. J Assist Reprod Genet. 2009;26:151–7.

    PubMed  Google Scholar 

  30. Mozaffarieh M, Schoetzau A, Sauter M, Grieshaber M, Orgül S, Golubnitschaja O, et al. Comet assay analysis of single-stranded DNA breaks in circulating leukocytes of glaucoma patients. Mol Vis. 2008;14:1584–8.

    PubMed  CAS  Google Scholar 

  31. Camargo M, Intasqui Lopes P, Del Giudice PT, Carvalho VM, Cardozo KH, Andreoni C, 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(1):33–46.

    PubMed  CAS  Google Scholar 

  32. Intasqui P, Camargo M, Del Giudice PT, Spaine DM, Carvalho VM, Cardozo KHM, Zylbersztejn DS, Bertolla RP (2013) Sperm nuclear DNA fragmentation rate is associated with differential protein expression and enriched functions in human seminal plasma. BJU Int

  33. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150:76–85.

    PubMed  CAS  Google Scholar 

  34. Cho CK, Smith CR, Diamandis EP. Amniotic fluid proteome analysis from down syndrome pregnancies for biomarker discovery. J Proteome Res. 2010;9(7):3574–82.

    PubMed  CAS  Google Scholar 

  35. Pan S, Chen R, Crispin DA, May D, Stevens T, McIntosh MW, et al. Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling. J Proteome Res. 2011;10(5):2359–576.

    PubMed  CAS  Google Scholar 

  36. Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2011;27(3):431–2.

    PubMed  CAS  Google Scholar 

  37. Martin A, Ochagavia ME, Rabasa LC, Miranda J, Fernandez-de-Cossio J, Bringas R. A new tool for gene network building, visualization and analysis. BMC Bioinforma. 2010;11:91.

    Google Scholar 

  38. da Huang W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13.

    Google Scholar 

  39. Quackenbush J. Extracting biology from high-dimensional biological data. J Exp Biol. 2007;210:1507–17.

    PubMed  CAS  Google Scholar 

  40. Kovac JR, Pastuszak AW, Lamb DJ. The use of genomics, proteomics, and metabolomics in identifying biomarkers of male infertility. Fertil Steril. 2013. doi:10.1016/j.fertnstert.2013.01.111.

    Google Scholar 

  41. Agarwal A, Sharma RK, Nallella KP, Thomas AJ, Alvarez JG, Sikka SC. Reactive oxygen species as an independent marker of male factor infertility. Fertil Steril. 2006;86(4):878–85.

    PubMed  CAS  Google Scholar 

  42. Baltz JM, Williams PO, Cone RA. Dense fibers protect mammalian sperm against damage. Biol Reprod. 1990;43:485–91.

    PubMed  CAS  Google Scholar 

  43. Haidl G, Becker A, Henkel R. Poor development of outer dense fibers as a major cause of tail abnormalities in the spermatozoa of asthenoteratozoospermic men. Hum Reprod. 1991;6:1431–8.

    PubMed  CAS  Google Scholar 

  44. Shao X, Murthy S, Demetrick DJ, van der Hoorn FA. Human outer dense fiber gene, ODF2, localizes to chromosome 9q34. Cytogenet Cell Genet. 1998;83(3–4):221–3.

    PubMed  CAS  Google Scholar 

  45. Pixton KL, Deeks ED, Flesch FM, Moseley FL, Björndahl L, Ashton PR, 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.

    PubMed  Google Scholar 

  46. Aitken RJ, Baker MA. The role of proteomics in understanding sperm cell biology. Int JAndrol. 2008;31:295–302.

    CAS  Google Scholar 

  47. Fontaine JM, Rest JS, Welsh MJ, Benndorf R. The sperm outer dense fiber protein is the 10th member of the superfamily of mammalian small stress proteins. Cell Stress Chaperones. 2003;8(1):62–9.

    PubMed  CAS  Google Scholar 

  48. Arrigo AP, Paul C, Ducasse C, Sauvageot O, Kretz-Remy C. Small stress proteins: modulation of intracellular redox state and protection against oxidative stress. Prog Mol Subcell Biol. 2002;28:171–84.

    PubMed  CAS  Google Scholar 

  49. Arrigo AP, Paul C, Ducasse C, Manero F, Kretz-Remy C, Virot S, et al. Small stress proteins: novel negative modulators of apoptosis induced independently of reactive oxygen species. Prog Mol Subcell Biol. 2002;28:185–204.

    PubMed  CAS  Google Scholar 

  50. Haslbeck M, Buchner J. Chaperone function of sHsps. Prog Mol Subcell Biol. 2002;28:37–59.

    PubMed  CAS  Google Scholar 

  51. Gene Ontology (GO:0050821), http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050821&session_id=5683amigo1336408572

  52. Nagamori I, Yabuta N, Fujii T, Tanaka H, Yomogida K, Nishimune Y, et al. Tisp40, a spermatid specific bZip transcription factor, functions by binding to the unfolded protein response element via the Rip pathway. Genes Cells. 2005;10(6):575–94.

    PubMed  CAS  Google Scholar 

  53. Eddy EM. Role of heat shock protein HSP70-2 in spermatogenesis. Rev Reprod. 1999;4:23–30.

    PubMed  CAS  Google Scholar 

  54. Redgrove KA, Nixon B, Baker MA, Hetherington L, Baker G, Liu DY, et al. The molecular chaperone HSPA2 plays a key role in regulating the expression of sperm surface receptors that mediate sperm-egg recognition. PLoS One. 2012;7:e50851.

    PubMed  CAS  Google Scholar 

  55. Lima SB, Cenedeze MA, Bertolla RP, Filho PA, Oehninger S, Cedenho AP. Expression of the HSPA2 gene in ejaculated spermatozoa from adolescents with and without varicocele. Fertil Steril. 2006;86(6):1659–963.

    PubMed  CAS  Google Scholar 

  56. Tesarik J, Greco E, Mendoza C. Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. Hum Reprod. 2004;19(3):611–5.

    PubMed  CAS  Google Scholar 

  57. Miki K, Willis WD, Brown PR, Goulding EH, Fulcher KD, Eddy EM. Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility. Dev Biol. 2002;248(2):331–42.

    PubMed  CAS  Google Scholar 

  58. Batruch I, Lecker I, Kagedan D, Smith CR, Mullen BJ, Grober E, et al. Proteomic analysis of seminal plasma from normal volunteers and post-vasectomy patients identifies over 2000 proteins and candidate biomarkers of the urogenital system. J Proteome Res. 2011;10(3):941–53.

    PubMed  CAS  Google Scholar 

  59. Cross NL, Mahasreshti P. Prostasome fraction of human seminal plasma prevents sperm from becoming acrosomally responsive to the agonist progesterone. Arch Androl. 1997;39(1):39–44.

    PubMed  CAS  Google Scholar 

  60. Park KH, Kim BJ, Kang J, Nam TS, Lim JM, Kim HT, Park JK, Kim YG, Chae SW, Kim UH (2011) Ca2+ signaling tools acquired from prostasomes are required for progesterone-induced sperm motility. Sci Signal 17;4(173):ra31

    Google Scholar 

  61. Pons-Rejraji H, Artonne C, Sion B, Brugnon F, Canis M, Janny L, et al. Prostasomes: inhibitors of capacitation and modulators of cellular signalling in human sperm. Int J Androl. 2011;34:568–80.

    PubMed  CAS  Google Scholar 

  62. Saez F, Motta C, Boucher D, Grizard G. Antioxidant capacity of prostasomes in human semen. Mol Hum Reprod. 1998;4:667–72.

    PubMed  CAS  Google Scholar 

  63. Ronquist KG, Ek B, Stavreus-Evers A, Larsson A, Ronquist G (2013) Human prostasomes express glycolytic enzymes with capacity for ATP production. Am J Physiol Endocrinol Metab

  64. Albarracín JL, Fernández-Novell JM, Ballester J, Rauch MC, Quintero-Moreno A, Peña A, et al. Gluconeogenesis-linked glycogen metabolism is important in the achievement of in vitro capacitation of dog spermatozoa in a medium without glucose. Biol Reprod. 2004;71(5):1437–45.

    PubMed  Google Scholar 

  65. Mukai C, Okuno M. Glycolysis plays a major role for adenosine triphosphate supplementation in mouse sperm flagellar movement. Biol Reprod. 2004;71(2):540–7.

    PubMed  CAS  Google Scholar 

  66. Marin S, Chiang K, Bassilian S, Lee WNP, Boros LG, Fernández-Novell JM, et al. Metabolic strategy of boar spermatozoa revealed by a metabolomic characterization. FEBS Lett. 2003;554:342–6.

    PubMed  CAS  Google Scholar 

  67. Mahadevan MM, Miller MM, Moutos DM. Absence of glucose decreases human fertilization and sperm movement characteristics in vitro. Hum Reprod. 1997;12:119–23.

    PubMed  CAS  Google Scholar 

  68. Williams AC, Ford WCL. The role of glucose in supporting motility and capacitation in human spermatozoa. J Androl. 2001;22(4):680–95.

    PubMed  CAS  Google Scholar 

  69. Rogers BJ, Perreault SD. Importance of glycolysable substrates for in vitro capacitation of human spermatozoa. Biol Reprod. 1990;43:1064–9.

    PubMed  CAS  Google Scholar 

  70. Argov N, Sklan D, Zeron Y, Roth Z. Association between seasonal changes in fatty-acid composition, expression of VLDL receptor and bovine sperm quality. Theriogenology. 2007;67:878–85.

    PubMed  CAS  Google Scholar 

  71. Beer-Ljubic B, Aladrovic J, Marenjak TS, Laskaj R, Majic-Balic I, Milinkovic-Tur S. Cholesterol concentration in seminal plasma as a predictive tool for quality semen evaluation. Theriogenology. 2009;72:1132–40.

    PubMed  CAS  Google Scholar 

  72. Amaral A, Castillo J, Estanyol JM, Ballescà JL, Ramalho-Santos J, Oliva R. Human sperm tail proteome suggests new endogenous metabolic pathways. Mol Cell Proteomics. 2013;12(2):330–42.

    PubMed  CAS  Google Scholar 

  73. Miki K, Qu W, Goulding EH, Willis WD, Bunch DO, Strader LF, et al. Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility. Proc Natl Acad Sci. 2004;101(47):16501–6.

    PubMed  CAS  Google Scholar 

  74. Spiropoulos J, Turnbull DM, Chinnery PF. Can mitochondrial DNA mutations cause sperm dysfunction? Mol Hum Reprod. 2002;8:719–21.

    PubMed  CAS  Google Scholar 

  75. Nakada K, Sato A, Yoshida K, Morita T, Tanaka H, Inoue S, Yonekawa H, Hayashi J (2006) Mitochondria-related male infertility. Proc Natl Acad Sci USA 10;103(41):15148–15153

    Google Scholar 

  76. Stendardi A, Focarelli R, Piomboni P, Palumberi D, Serafini F, Ferramosca A, et al. Evaluation of mitochondrial respiratory efficiency during in vitro capacitation of human spermatozoa. Int J Androl. 2011;34(3):247–55.

    PubMed  CAS  Google Scholar 

  77. Ruiz-Pesini E, Diez C, Lapeña AC, Pérez-Martos A, Montoya J, Alvarez E, et al. Correlation of sperm motility with mitochondrial enzymatic activities. Clin Chem. 1998;44(8Pt1):1616–20.

    PubMed  CAS  Google Scholar 

  78. Narisawa S, Hecht NB, Goldberg E, Boatright KM, Reed JC, Millán JL. Testis-specific cytochrome c-null mice produce functional sperm but undergo early testicular atrophy. Mol Cell Biol. 2002;15:5554–62.

    Google Scholar 

  79. Ferramosca A, Focarelli R, Piomboni P, Coppola L, Zara V. Oxygen uptake by mitochondria in demembranated human spermatozoa: a reliable tool for the evaluation of sperm respiratory efficiency. Int J Androl. 2008;31(3):337–45.

    PubMed  CAS  Google Scholar 

  80. UniProt Entry Q8TDB8, http://www.uniprot.org/uniprot/Q8TDB8

  81. Wang X, Sharma RK, Gupta A, George V, Thomas AJ, Falcone T, et al. Alterations in mitochondria membrane potential and oxidative stress in infertile men: a prospective observational study. Fertil Steril. 2003;80:844–50.

    PubMed  Google Scholar 

  82. Bergamo P, Balestrieri M, Cammarota G, Guardiola J, Abrescia P. CD4-mediated anchoring of the seminal antigen gp17 onto the spermatozoon surface. Hum Immunol. 1997;58:30–41.

    PubMed  CAS  Google Scholar 

  83. Thacker S, Yadav SP, Sharma RK, Kashou A, Willard B, Zhang D, Agarwal A (2011) Evaluation of sperm proteins in infertile men: a proteomic approach. Fertil Steril 30;95(8):2745–2748

    Google Scholar 

  84. Ma T, Keller JA, Yu X. RNF8-dependent histone ubiquitination during DNA damage response and spermatogenesis. Acta Biochim Biophys Sin. 2011;43(5):339–45.

    PubMed  CAS  Google Scholar 

  85. Chakravarty S, Bansal P, Sutovsky P, Gupta SK. Role of proteasomal activity in the induction of acrosomal exocytosis in human spermatozoa. Reprod Biomed Online. 2008;16:391–400.

    PubMed  CAS  Google Scholar 

  86. Kong M, Diaz ES, Morales P. Participation of the human sperm proteasome in the capacitation process and its regulation by protein kinase A and tyrosine kinase. Biol Reprod. 2009;80(5):1026–35.

    PubMed  CAS  Google Scholar 

  87. Yi YJ, Zimmerman SW, Manandhar G, Odhiambo JF, Kennedy C, Jonáková V, et al. Ubiquitin-activating enzyme (UBA1) is required for sperm capacitation, acrosomal exocytosis and sperm-egg coat penetration during porcine fertilization. Int J Androl. 2012;35(2):196–210.

    PubMed  CAS  Google Scholar 

  88. Sutovsky P, Moreno R, Ramalho-Santos J, Dominko T, Thompson WE, Schatten G. A putative, ubiquitin-dependent mechanism for the recognition and elimination of defective spermatozoa in the mammalian epididymis. J Cell Sci. 2001;114:1665–75.

    PubMed  CAS  Google Scholar 

  89. Yoshida H, Matsui T, Hosokawa N, Kaufman JR, Nagata K, Mori K. A time-dependent phase shift in the mammalian unfolded protein response. Dev Cell. 2003;4:265–71.

    PubMed  CAS  Google Scholar 

  90. Sylvester SR, Morales C, Oko R, Griswold MD. Localization of sulfated glycoprotein-2 (clusterin) on spermatozoa and in the reproductive tract of the male rat. Biol Reprod. 1991;45:195–207.

    PubMed  CAS  Google Scholar 

  91. Buttyan R, Olsson CA, Pintar J, Chang C, Bandyk M, Ng PY, et al. Induction of the TRPM-2 gene in cells undergoing programmed death. Mol Cell Biol. 1989;9:3473–81.

    PubMed  CAS  Google Scholar 

  92. Fritz IB, Burdzy K, Setchell B, Blaschuk O. Ram rete testis fluid contains a protein (clusterin) which influences cell-cell interaction in vitro. Biol Reprod. 1983;28:1173–88.

    PubMed  CAS  Google Scholar 

  93. Murphy BF, Kirszbaum L, Walker ID, d’Apice AJ. SP-40, 40, a newly identified normal human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis. J Clin Invest. 1988;81:1858–64.

    PubMed  CAS  Google Scholar 

  94. Jenne DE, Lowin B, Peitsch MC, Böttcher A, Schmitz G, Tschopp J. Clusterin (complement lysis inhibitor) forms a high density lipoprotein complex with apolipoprotein A-I in human plasma. J Biol Chem. 1991;266:11030–6.

    PubMed  CAS  Google Scholar 

  95. Ibrahim NM, Gilbert GR, Loseth KL, Crabo BG. Correlation between clusterin-positive spermatozoa determined by flow cytometry in bull semen and fertility. J Androl. 2000;21:887–94.

    PubMed  CAS  Google Scholar 

  96. O’Bryan MK, Murphy BF, Liu DY, Clarke GN, Baker HW. The use of anticlusterin monoclonal antibodies for the combined assessment of human sperm morphology and acrosome integrity. Hum Reprod. 1994;9:1490–6.

    PubMed  Google Scholar 

  97. Novak S, Smith TA, Paradis F, Burwash L, Dyck MK, Foxcroft GR, et al. Biomarkers of in vivo fertility in sperm and seminal plasma of fertile stallions. Theriogenology. 2010;74:956–67.

    PubMed  CAS  Google Scholar 

  98. Huleihel M, Lunenfeld E, Horowitz S, Levy A, Potashnik G, Glezerman M. Production of interleukin-1-like molecules by human sperm cells. Fertil Steril. 2000;73(6):1132–7.

    PubMed  CAS  Google Scholar 

  99. Austgulen R, Arntzen KJ, Vatten LJ, Kahn J, Sunde A. Detection of cytokines (interleukin-1, interleukin-6, transforming growth factor-beta) and soluble tumor necrosis factor receptors in embryo culture fluids during in-vitro fertilization. Hum Reprod. 1995;10(1):171–6.

    PubMed  CAS  Google Scholar 

  100. Cheng EH, Sheiko TV, Fisher JK, Craigen WJ, Korsmeyer SJ. VDAC2 inhibits BAK activation and mitochondrial apoptosis. Science. 2003;301(5632):513–7.

    PubMed  CAS  Google Scholar 

  101. Liu B, Wang P, Wang Z, Jia Y, Niu X, Wang W, et al. Analysis and difference of voltage-dependent anion channel mRNA in ejaculated spermatozoa from normozoospermic fertile donors and infertile patients with idiopathic asthenozoospermia. J Assist Reprod Genet. 2010;27:719–24.

    PubMed  Google Scholar 

  102. Hinsch K-D, De Pinto V, Aires VA, Schneider X, Messina A, Hinsch E. Voltage-dependent anion-selective channels VDAC2 and VDAC3 are abundant proteins in bovine outer dense fibers, a cytoskeletal component of the sperm flagellum. J Biol Chem. 2004;279(15):15281–8.

    PubMed  CAS  Google Scholar 

  103. Alvarez JG, Storey BT. Role of glutathione peroxidase in protecting mammalian spermatozoa from loss of motility caused by spontaneous lipid peroxidation. Gamete Res. 1989;23:77–90.

    PubMed  CAS  Google Scholar 

  104. Colagar AH, Marzony ET. Ascorbic Acid in human seminal plasma: determination and its relationship to sperm quality. J Clin Biochem Nutr. 2009;45:144–9.

    PubMed  CAS  Google Scholar 

  105. Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79:829–43.

    PubMed  Google Scholar 

  106. Sharma RK, Agarwal A. Role of reactive oxygen species in male infertility. Urology. 1996;48:835–50.

    PubMed  CAS  Google Scholar 

  107. Ichikawa T, Oeda T, Ohmori H, Schill W-B. Reactive oxygen species influence the acrosome reaction but not acrosin activity in human spermatozoa. International J Androl. 1999;22:37–42.

    CAS  Google Scholar 

  108. Tremellen K. Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update. 2008;14:243–58.

    PubMed  CAS  Google Scholar 

  109. Lin YN, Roy A, Yan W, Burns KH, Matzuk MM. Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Mol Cell Biol. 2007;27(19):6794–805.

    PubMed  CAS  Google Scholar 

  110. Nixon B, Aitken RJ, McLaughlin EA. New insights into the molecular mechanisms of sperm–egg interaction. Cell Mol Life Sci. 2007;64:1805–23.

    PubMed  CAS  Google Scholar 

  111. Diamandis EP, Arnett WP, Foussias G, Pappas H, Ghandi S, Melegos DN, et al. Seminal plasma biochemical markers and their association with semen analysis findings. Urology. 1999;53(3):596–603.

    PubMed  CAS  Google Scholar 

  112. Szecsi PB, Dalgaard D, Stakemann G, Wagner G, Foltmann B. T he concentration of pepsinogen C in human semen and the physiological activation of zymogen in the vagina. Biol Reprod. 1989;40(3):653–9.

    PubMed  CAS  Google Scholar 

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Acknowledgements

The authors wish to thank Fleury/Finep for research funding and financial support. Ms. Intasqui was recipient of a scholarship from the Fundação de Amparo à Pesquisa no Estado de Sao Paulo (FAPESP process number 2011/00385-4).

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Correspondence to Paula Intasqui.

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Capsule Sperm DNA fragmentation is associated with differential protein expression and biological functions in viable sperm. These proteins may be potentially used as biomarkers for sperm DNA integrity.

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Intasqui, P., Camargo, M., Del Giudice, P.T. et al. Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation. J Assist Reprod Genet 30, 1187–1202 (2013). https://doi.org/10.1007/s10815-013-0054-6

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  • DOI: https://doi.org/10.1007/s10815-013-0054-6

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