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Chapter 25 - Future Developments: Sperm Proteomics

Published online by Cambridge University Press:  05 April 2021

Ashok Agarwal
The Cleveland Clinic Foundation, Cleveland, OH
Ralf Henkel
University of the Western Cape, South Africa
Ahmad Majzoub
Hamad Medical Corporation, Doha
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Spermatozoa are mature male gametes that are produced in the testes of a healthy man by spermatogenesis, with further maturation of sperm taking place during their transit through the epididymis. In the human, approximately 20 to 240 million sperm are produced per day [1]. Unlike other somatic cells present in the human body, spermatozoa contain a head, neck, mid-piece and tail region. The head region contains the genetic material which is transferred to the oocyte during the fertilization process. Apart from DNA, spermatozoa also deliver additional subcellular materials such as oocyte activating factors, RNA, microRNAs and exosomal proteins that are essential for the development of the oocyte into a zygote.

Publisher: Cambridge University Press
Print publication year: 2021

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Plant, TM, Zeleznik, AJ. (2014). Knobil and Neill's Physiology of Reproduction. Amsterdam: Elsevier Academic Press.Google Scholar
World Health Organization. (2010). WHO Laboratory Manual for the Examination and Processing of Human Semen. Geneva: The WHO Press.Google Scholar
Agarwal, A, Gupta, S, Sharma, R. (2016). Oxidation–reduction potential measurement in ejaculated semen samples. In Agarwal, A, Gupta, S and Sharma, R, eds., Andrological Evaluation of Male Infertility: A Laboratory Guide. London: Springer International Publishing, pp. 165–70.CrossRefGoogle Scholar
Agarwal, A, Sharma, R, Roychoudhury, S, Du Plessis, S, Sabanegh, E. MiOXSYS: a novel method of measuring oxidation reduction potential in semen and seminal plasma. Fertil Steril 2016; 106: 566–73.e510.CrossRefGoogle ScholarPubMed
Bracke, A, Peeters, K, Punjabi, U, Hoogewijs, D, Dewilde, S. A search for molecular mechanisms underlying male idiopathic infertility. Reprod BioMed Online 2018; 36: 327–39.CrossRefGoogle ScholarPubMed
Amaral, A, Lourenço, B, Marques, M, Ramalho-Santos, J. Mitochondria functionality and sperm quality. Reproduction 2013; 146: R163R174.CrossRefGoogle ScholarPubMed
Amaral, A, Castillo, J, Estanyol, JM, Ballesca, JL, Ramalho-Santos, J, Oliva, R. Human sperm tail proteome suggests new endogenous metabolic pathways. Mol Cell Proteom 2013; 12: 330–42.CrossRefGoogle ScholarPubMed
Amaral, A, Paiva, C, Attardo Parrinello, C, Estanyol, JM, Ballescà, JLS, Ramalho-Santos, JO, Oliva, R. Identification of proteins involved in human sperm motility using high-throughput differential proteomics. J Proteome Res 2014; 13: 5670–84.CrossRefGoogle ScholarPubMed
Intasqui, P, Camargo, M, Del Giudice, PT, Spaine, DM, Carvalho, VM, Cardozo, KHM, Cedenho, AP, Bertolla, RP. Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation. J Assist Reprod Genet 2013; 30: 1187–202.CrossRefGoogle ScholarPubMed
Martínez‐Heredia, J, Estanyol, JM, Ballescà, JL, Oliva, R. Proteomic identification of human sperm proteins. Proteomics 2006; 6: 4356–69.CrossRefGoogle ScholarPubMed
Wang, S, Wang, W, Xu, Y, Tang, M, Fang, J, Sun, H, Sun, Y, Gu, M, Liu, Z, Zhang, Z. Proteomic characteristics of human sperm cryopreservation. Proteomics 2014; 14: 298310.CrossRefGoogle ScholarPubMed
Wang, XM, Xiang, Z, Fu, Y, Wu, HL, Zhu, WB, Fan, LQ. Comparative proteomics reveal the association between SPANX proteins and clinical outcomes of artificial insemination with donor sperm. Scientific Reports 2018; 8: 6850.CrossRefGoogle ScholarPubMed
Panner Selvam, MK, Agarwal, A, Dias, TR, Martins, AD, Baskaran, S, Samanta, L. Molecular pathways associated with sperm biofunction are not affected by the presence of round cell and leukocyte proteins in human sperm proteome. J Proteome Res 2018; 18: 1191−7.Google Scholar
Panner Selvam, MK, Agarwal, A, Dias, TR, Martins, AD, Samanta, L. Presence of round cells proteins do not interfere with identification of human sperm proteins from frozen semen samples by LC-MS/MS. Int J Mol Sci 2019; 20: 314.CrossRefGoogle Scholar
Glish, GL, Vachet, RW. The basics of mass spectrometry in the twenty-first century. Nat Rev Drug Discov 2003; 2: 140.CrossRefGoogle ScholarPubMed
Zhou, T, Zhou, Z-M, Guo, X-J. Bioinformatics for spermatogenesis: annotation of male reproduction based on proteomics. Asian J Androl 2013; 15: 594.CrossRefGoogle ScholarPubMed
Lan, N, Montelione, GT, Gerstein, M. Ontologies for proteomics: towards a systematic definition of structure and function that scales to the genome level. Curr Opin Chem Biol 2003; 7: 4454.CrossRefGoogle ScholarPubMed
Agarwal, A, Durairajanayagam, D, Halabi, J, Peng, J, Vazquez-Levin, M. Proteomics, oxidative stress and male infertility. Reprod BioMed Online 2014; 29: 3258.CrossRefGoogle ScholarPubMed
Johnston, DS, Wooters, J, Kopf, GS, Qiu, Y, Roberts, KP. Analysis of the human sperm proteome. Ann NY Acad Sci 2005; 1061: 190202.CrossRefGoogle ScholarPubMed
Baker, MA, Reeves, G, Hetherington, L, Müller, J, Baur, I, Aitken, RJ. Identification of gene products present in Triton X-100 soluble and insoluble fractions of human spermatozoa lysates using LC-MS/MS analysis. Proteom Clin Appl 2007; 1: 524–32.CrossRefGoogle ScholarPubMed
Gilany, K, Lakpour, N, Vafakhah, M, Sadeghi, MR. The profile of human sperm proteome: a mini-review. J Reprod Infertil 2011; 12: 193–9.Google ScholarPubMed
Baker, MA, Naumovski, N, Hetherington, L, Weinberg, A, Velkov, T, Aitken, RJ. Head and flagella subcompartmental proteomic analysis of human spermatozoa. Proteomics 2013;13: 6174.CrossRefGoogle ScholarPubMed
Nixon, B, Mitchell, LA, Anderson, AL, Mclaughlin, EA, O'Bryan, MK, Aitken, RJ. Proteomic and functional analysis of human sperm detergent resistant membranes. J Cell Physiol 2011; 226: 2651–65.CrossRefGoogle ScholarPubMed
de Mateo, S, Castillo, J, Estanyol, JM, Ballescà, JL, Oliva, R. Proteomic characterization of the human sperm nucleus. Proteomics 2011; 11: 2714–26.CrossRefGoogle ScholarPubMed
de Mateo, S, Martínez-Heredia, J, Estanyol, JM, Domíguez-Fandos, D, Vidal-Taboada, JM, Ballescà, JL, Oliva, R. Marked correlations in protein expression identified by proteomic analysis of human spermatozoa. Proteomics 2007; 7: 4264–77.CrossRefGoogle ScholarPubMed
Kupis, Ł, Dobroński, PA, Radziszewski, P. Varicocele as a source of male infertilitycurrent treatment techniques. Cent European J Urol 2015; 68: 365–70.CrossRefGoogle ScholarPubMed
Hosseinifar, H, Gourabi, H, Salekdeh, GH, Alikhani, M, Mirshahvaladi, S, Sabbaghian, M, Modarresi, T, Gilani, MAS. Study of sperm protein profile in men with and without varicocele using two-dimensional gel electrophoresis. Urology 2013; 81: 293300.CrossRefGoogle ScholarPubMed
Agarwal, A, Sharma, R, Durairajanayagam, D, Ayaz, A, Cui, Z, Willard, B, Gopalan, B, Sabanegh, E. Major protein alterations in spermatozoa from infertile men with unilateral varicocele. Reprod Biol Endocrinol 2015; 13: 8.CrossRefGoogle ScholarPubMed
Agarwal, A, Sharma, R, Durairajanayagam, D, Cui, Z, Ayaz, A, Gupta, S, Willard, B, Gopalan, B, Sabanegh, E. Spermatozoa protein alterations in infertile men with bilateral varicocele. Asian J Androl 2016; 18: 4353.CrossRefGoogle ScholarPubMed
Agarwal, A, Sharma, R, Durairajanayagam, D, Cui, Z, Ayaz, A, Gupta, S, Willard, B, Gopalan, B, Sabanegh, E. Differential proteomic profiling of spermatozoal proteins of infertile men with unilateral or bilateral varicocele. Urology 2015; 85: 580–8.CrossRefGoogle ScholarPubMed
Agarwal, A, Sharma, R, Samanta, L, Durairajanayagam, D, Sabanegh, E. Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility. Asian J Androl 2016; 18: 282–91.CrossRefGoogle ScholarPubMed
Samanta, L, Agarwal, A, Swain, N, Sharma, R, Gopalan, B, Esteves, SC, Durairajanayagam, D, Sabanegh, E. Proteomic signatures of sperm mitochondria in varicocele: clinical use as biomarkers of varicocele associated infertility. J Urol 2018; 200: 414–22.CrossRefGoogle ScholarPubMed
Siegel, RL, Miller, KD, statistics, Jemal A. Cancer. CA Cancer J Clin 2019; 69: 734.CrossRefGoogle Scholar
Rives, N, Perdrix, A, Hennebicq, S, Saïas‐Magnan, J, Melin, MC, Berthaut, I, Barthélémy, C, Daudin, M, Szerman, E, Bresson, JL. The semen quality of 1158 men with testicular cancer at the time of cryopreservation: results of the French National CECOS Network. J Androl 2012; 33: 1394–401.CrossRefGoogle ScholarPubMed
Dias, TR, Agarwal, A, Pushparaj, PN, Ahmad, G, Sharma, R. New insights on the mechanisms affecting fertility in men with non-seminoma testicular cancer before cancer therapy. World J Mens Health 2018; 38: 198207.CrossRefGoogle Scholar
Dias, TR, Agarwal, A, Pushparaj, PN, Ahmad, G, Sharma, R. Reduced semen quality in patients with testicular cancer seminoma is associated with alterations in the expression of sperm proteins. Asian J Androl 2020; 22: 8893.Google ScholarPubMed
Agarwal, A, Tvrda, E, Sharma, R, Gupta, S, Ahmad, G, Sabanegh, ES. Spermatozoa protein profiles in cryobanked semen samples from testicular cancer patients before treatment. Fertil Steril 2015; 104: e260.CrossRefGoogle Scholar
Panner Selvam, MK, Agarwal, A, Pushparaj, PN. Altered molecular pathways in the proteome of cryopreserved sperm in testicular cancer patients before treatment. Int J Mol Sci 2019; 20: 677.CrossRefGoogle Scholar
Panner Selvam, MK, Agarwal, A, Pushparaj, PN. A quantitative global proteomics approach to understanding the functional pathways dysregulated in the spermatozoa of asthenozoospermic testicular cancer patients. Andrology 2019; 7: 454–62.Google ScholarPubMed
Hamada, A, Esteves, SC, Agarwal, A. Unexplained male infertility: potential causes and management. Hum Androl 2011; 1: 216.CrossRefGoogle Scholar
Wallach, EE, Moghissi, KS, Wallach, EE. Unexplained infertility. Fertil Steril 1983; 39: 521.CrossRefGoogle Scholar
Frapsauce, C, Pionneau, C, Bouley, J, Delarouziere, V, Berthaut, I, Ravel, C, Antoine, J-M, Soubrier, F, Mandelbaum, J. Proteomic identification of target proteins in normal but nonfertilizing sperm. Fertil Steril 2014; 102: 372–80.CrossRefGoogle ScholarPubMed
Azpiazu, R, Amaral, A, Castillo, J, Estanyol, JM, Guimerà, M, Ballescà, JL, Balasch, J, Oliva, R. High-throughput sperm differential proteomics suggests that epigenetic alterations contribute to failed assisted reproduction. Hum Reprod 2014; 29: 1225–37.CrossRefGoogle ScholarPubMed
Légaré, C, Droit, A, Fournier, F, Bourassa, S, Force, A, Cloutier, F, Tremblay, R, Sullivan, R. Investigation of male infertility using quantitative comparative proteomics. J Proteom Res 2014; 13: 5403–14.CrossRefGoogle ScholarPubMed
Xu, W, Hu, H, Wang, Z, Chen, X, Yang, F, Zhu, Z, Fang, P, Dai, J, Wang, L, Shi, H et al. Proteomic characteristics of spermatozoa in normozoospermic patients with infertility. J Proteom 2012; 75: 5426–36.CrossRefGoogle ScholarPubMed
Panner Selvam, MK, Agarwal, A, Pushparaj, PN, Baskaran, S, Bendou, H. Sperm proteome analysis and identification of fertility-associated biomarkers in unexplained male infertility. Genes 2019; 10: 522.CrossRefGoogle ScholarPubMed
Giacomini, E, Ura, B, Giolo, E, Luppi, S, Martinelli, M, Garcia, RC, Ricci, G. Comparative analysis of the seminal plasma proteomes of oligoasthenozoospermic and normozoospermic men. Reprod Biomed Online 2015; 30: 522–31.CrossRefGoogle ScholarPubMed
Herwig, R, Knoll, C, Planyavsky, M, Pourbiabany, A, Greilberger, J, Bennett, KL. Proteomic analysis of seminal plasma from infertile patients with oligoasthenoteratozoospermia due to oxidative stress and comparison with fertile volunteers. Fertil Steril 2013; 100: 355–66.e352.CrossRefGoogle ScholarPubMed
Liu, X, Wang, W, Zhu, P, Wang, J, Wang, Y, Wang, X, Liu, J, Li, N, Lin, C, Liu, F. In-depth quantitative proteome analysis of seminal plasma from men with oligoasthenozoospermia and normozoospermia. Reprod Biomed Online 2018; 37: 467–79.CrossRefGoogle ScholarPubMed
Martínez-Heredia, J, de Mateo, S, Vidal-Taboada, JM, Ballescà, JL, Oliva, R. Identification of proteomic differences in asthenozoospermic sperm samples. Hum Reprod 2008; 23: 783–91.CrossRefGoogle ScholarPubMed
Nowicka-Bauer, K, Lepczynski, A, Ozgo, M, Kamieniczna, M, Fraczek, M, Stanski, L, Olszewska, M, Malcher, A, Skrzypczak, W, Kurpisz, M. Sperm mitochondrial dysfunction and oxidative stress as possible reasons for isolated asthenozoospermia. J Physiol Pharmacol 2018; 69(3). doi: 10.26402/jpp.2018.3.05CrossRefGoogle Scholar
Parte, PP, Rao, P, Redij, S, Lobo, V, D'Souza, SJ, Gajbhiye, R, Kulkarni, V. Sperm phosphoproteome profiling by ultra performance liquid chromatography followed by data independent analysis (LC–MSE) reveals altered proteomic signatures in asthenozoospermia. J Proteom 2012; 75: 5861–71.CrossRefGoogle Scholar
Saraswat, M, Joenväärä, S, Jain, T, Tomar, AK, Sinha, A, Singh, S, Yadav, S, Renkonen, R. Human spermatozoa quantitative proteomic signature classifies normo- and asthenozoospermia. Mol Cell Proteom 2017; 16: 5772.CrossRefGoogle ScholarPubMed
Sinha, A, Singh, V, Singh, S, Yadav, S. Proteomic analyses reveal lower expression of TEX40 and ATP6V0A2 proteins related to calcium ion entry and acrosomal acidification in asthenozoospermic males. Life Sciences 2019; 218: 81–8.CrossRefGoogle ScholarPubMed
Siva, AB, Kameshwari, DB, Singh, V, Pavani, K, Sundaram, CS, Rangaraj, N, Deenadayal, M, Shivaji, S. Proteomics-based study on asthenozoospermia: differential expression of proteasome alpha complex. Mol Hum Reprod 2010; 16(7): 452–62. doi: 10.1093/molehr/gaq009CrossRefGoogle Scholar
Zhao, C, Huo, R, Wang, F-Q, Lin, M, Zhou, Z-M, Sha, J-H. Identification of several proteins involved in regulation of sperm motility by proteomic analysis. Fertil Steril 2007; 87: 436–8.CrossRefGoogle ScholarPubMed
Cao, X, Cui, Y, Zhang, X, Lou, J, Zhou, J, Bei, H, Wei, R. Proteomic profile of human spermatozoa in healthy and asthenozoospermic individuals. Reprod Biol Endocrinol 2018;16: 16.CrossRefGoogle ScholarPubMed
Swain, N, Samanta, L, Agarwal, A, Kumar, S, Dixit, A, Gopalan, B, Durairajanayagam, D, Sharma, R, Puspharaj, PN, Baskaran, S. Aberrant upregulation of compensatory redox molecular machines may contribute to sperm dysfunction in infertile men with unilateral varicocele: a proteomic insight. Antioxid Redox Signal 2019; 32: 504–21.Google ScholarPubMed
Hashemitabar, M, Sabbagh, S, Orazizadeh, M, Ghadiri, A, Bahmanzadeh, M. A proteomic analysis on human sperm tail: comparison between normozoospermia and asthenozoospermia. J Assist Reprod Genet 2015; 32: 853–63.CrossRefGoogle ScholarPubMed
Liao, TT, Xiang, Z, Zhu, WB, Fan, LQ. Proteome analysis of round-headed and normal spermatozoa by 2-D fluorescence difference gel electrophoresis and mass spectrometry. Asian J Androl 2009; 11: 683–93.CrossRefGoogle ScholarPubMed
Dam, AHDM, Feenstra, I, Westphal, JR, Ramos, L, van Golde, RJT, Kremer, JAM. Globozoospermia revisited. Hum Reprod Update 2006; 13: 6375.CrossRefGoogle ScholarPubMed
Kovac, JR, Lipshultz, LI. The significance of insulin-like factor 3 as a marker of intratesticular testosterone. Fertil Steril 2013; 99: 66–7.CrossRefGoogle ScholarPubMed
Oehninger, S, Franken, DR, Ombelet, W. Sperm functional tests. Fertil Steril 2014; 102: 1528–33.CrossRefGoogle ScholarPubMed
Hamada, A, Sharma, R, du Plessis, SS, Willard, B, Yadav, SP, Sabanegh, E, Agarwal, A. Two-dimensional differential in-gel electrophoresis-based proteomics of male gametes in relation to oxidative stress. Fertil Steril 2013; 99: 1216–26.e1212.CrossRefGoogle ScholarPubMed
Sharma, R, Agarwal, A, Mohanty, G, Hamada, AJ, Gopalan, B, Willard, B, Yadav, S, du Plessis, S. Proteomic analysis of human spermatozoa proteins with oxidative stress. Reprod Biol Endocrinol 2013; 11: 48.CrossRefGoogle ScholarPubMed
Ayaz, A, Agarwal, A, Sharma, R, Kothandaraman, N, Cakar, Z, Sikka, S. Proteomic analysis of sperm proteins in infertile men with high levels of reactive oxygen species. Andrologia 2018; 50: e13015.CrossRefGoogle ScholarPubMed
Hosseinifar, H, Sabbaghian, M, Nasrabadi, D, Modarresi, T, Dizaj, AV, Gourabi, H, Gilani, MA. 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.CrossRefGoogle ScholarPubMed
Agarwal, A, Sharma, R, Samanta, L, Durairajanayagam, D, Sabanegh, E. Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility. Asian J Androl 2016; 18: 282–91.CrossRefGoogle ScholarPubMed
Intasqui, P, Camargo, M, Antoniassi, MP, Cedenho, AP, Carvalho, VM, Cardozo, KHM, Zylbersztejn, DS, Bertolla, RP. Association between the seminal plasma proteome and sperm functional traits. Fertil Steril 2016; 105: 617–28.CrossRefGoogle ScholarPubMed
Schiza, CG, Jarv, K, Diamandis, EP, Drabovich, AP. An emerging role of TEX101 protein as a male infertility biomarker. EJIFCC 2014; 25: 926.Google ScholarPubMed
Bieniek, JM, Drabovich, AP, Lo, KC. Seminal biomarkers for the evaluation of male infertility. Asian J Androl 2016; 18: 426–33.CrossRefGoogle ScholarPubMed
Huang, Z, Lin, L, Gao, Y, Chen, Y, Yan, X, Xing, J, Hang, W. Bladder cancer determination via two urinary metabolites: a biomarker pattern approach. Mol Cell Proteom 2011; 10: M111.007922.CrossRefGoogle ScholarPubMed
Zhang, J, Mu, X, Xia, Y, Martin, FL, Hang, W, Liu, L, Tian, M, Huang, Q, Shen, H. Metabolomic analysis reveals a unique urinary pattern in normozoospermic infertile men. J Proteom Res 2014; 13: 3088–99.CrossRefGoogle ScholarPubMed

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