Exosome Composition and Seminal Plasma Proteome: A Promising Source of Biomarkers of Male Infertility
Abstract
:1. Introduction
2. Exosomes in the Male Reproductive Tract: Their Potential Role in Sperm Physiology
3. Proteomic Landscape of SP: A Potential Indicator of Sperm Dysfunction
3.1. The SP Proteome
3.2. Analysis of Human SP Proteome
3.3. SP Candidate Biomarkers of Male Infertility
3.3.1. SP Candidate Biomarkers for Azoospermia
3.3.2. SP Candidate Biomarkers for Asthenozoospermia, Oligozoospermia and Teratozoospermia
3.3.3. SP Candidate Biomarkers for Semen with High Reactive Oxygen Species (ROS) Levels
3.3.4. SP Candidate Biomarkers for Varicocele
3.3.5. SP Candidate Biomarkers for Primary and Secondary Infertility
4. Conclusions and Future Perspectives
Funding
Acknowledgments
Conflicts of Interest
References
- Sendler, E.; Johnson, G.D.; Mao, S.; Goodrich, R.J.; Diamond, M.P.; Hauser, R.; Krawetz, S.A. Stability, delivery and functions of human sperm RNAs at fertilization. Nucleic Acids Res. 2013, 41, 4104–4117. [Google Scholar] [CrossRef] [PubMed]
- Rodriguez-Martinez, H.; Kvist, U.; Ernerudh, J.; Sanz, L.; Calvete, J.J. Seminal plasma proteins: What role do they play? Am. J. Reprod. Immunol. 2011, 66, 11–22. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Samanta, L.; Parida, R.; Dias, T.R.; Agarwal, A. The enigmatic seminal plasma: A proteomics insight from ejaculation to fertilization. Reprod. Biol. Endocrinol. 2018, 16, 41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lilja, H.; Oldbring, J.; Rannevik, G.; Laurell, C.B. Seminal vesicle-secreted proteins and their reactions during gelation and liquefaction of human semen. J. Clin. Investig. 1987, 80, 281–285. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aalberts, M.; Stout, T.A.; Stoorvogel, W. Prostasomes: Extracellular vesicles from the prostate. Reproduction 2014, 147, R1–R14. [Google Scholar] [CrossRef] [Green Version]
- Jodar, M.; Soler-Ventura, A.; Oliva, R. Molecular Biology of Reproduction and Development Research Group. Semen proteomics and male infertility. J. Proteom. 2017, 162, 125–134. [Google Scholar] [CrossRef]
- Johnson, M.H. Sperm and eggs. In Essential Reproduction, 8th ed.; Wiley Blackwell: Hoboken, NJ, USA, 2018; pp. 183–196. [Google Scholar]
- World Health Organization (WHO). WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction, 4th ed.; Cambridge University Press: New York, NY, USA, 1999. [Google Scholar]
- Vasan, S.S. Semen analysis and sperm function tests: How much to test? Indian J. Urol. 2011, 27, 41–48. [Google Scholar] [CrossRef]
- Drabovich, A.P.; Saraon, P.; Jarvi, K.; Diamandis, E.P. Seminal plasma as a diagnostic fluid for male reproductive system disorders. Nat. Rev. Urol. 2014, 11, 278–288. [Google Scholar] [CrossRef]
- Milardi, D.; Grande, G.; Vincenzoni, F.; Castagnola, M.; Marana, R. Proteomics of human seminal plasma: Identification of biomarker candidates for fertility and infertility and the evolution of technology. Mol. Reprod. Dev. 2013, 80, 350–357. [Google Scholar] [CrossRef]
- Sullivan, R.; Saez, F. Epididymosomes, prostasomes and liposomes; their role in mammalian male reproductive physiology. Reproduction 2013, 146, R21–R35. [Google Scholar] [CrossRef] [Green Version]
- Raposo, G.; Nijman, H.W.; Stoorvogel, W.; Liejendekker, R.; Harding, C.V.; Melief, C.J.; Geuze, H.J. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 1996, 183, 1161–1172. [Google Scholar] [CrossRef] [PubMed]
- Mathias, R.A.; Lim, J.W.; Ji, H.; Simpson, R.J. Isolation of extracellular membranous vesicles for proteomic analysis. Methods Mol. Biol. 2009, 528, 227–242. [Google Scholar] [PubMed]
- Théry, C.; Boussac, M.; Véron, P.; Ricciardi-Castagnoli, P.; Raposo, G.; Garin, J.; Amigorena, S. Proteomic analysis of dendritic cell-derived exosomes: A secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol. 2001, 166, 7309–7318. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Keerthikumar, S.; Chisanga, D.; Ariyaratne, D.; Al Saffar, H.; Anand, S.; Zhao, K.; Samuel, M.; Pathan, M.; Jois, M.; Chilamkurti, N.; et al. ExoCarta: A web-based compendium of exosomal cargo. J. Mol. Biol. 2016, 428, 688–692. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Belleannée, C.; Calvo, É.; Caballero, J.; Sullivan, R. Epididymosomes convey different repertoires of microRNAs throughout the bovine epididymis. Biol. Reprod. 2013, 89, 30. [Google Scholar] [CrossRef]
- Conine, C.C.; Sun, F.; Song, L.; Rivera-Pérez, J.A.; Rando, O.J. Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice. Dev. Cell 2018, 46, 470.e3–480.e3. [Google Scholar] [CrossRef] [Green Version]
- Sharma, U.; Sun, F.; Conine, C.C.; Reichholf, B.; Kukreja, S.; Herzog, V.A.; Ameres, S.L.; Rando, O.J. Small RNAs are trafficked from the epididymis to developing mammalian sperm. Dev. Cell 2018, 46, 481–494.e6. [Google Scholar] [CrossRef]
- Leahy, T.; Rickard, J.P.; Pini, T.; Gadella, B.M.; de Graaf, S.P. Quantitative Proteomic Analysis of Seminal Plasma, Sperm Membrane Proteins, and Seminal Extracellular Vesicles Suggests Vesicular Mechanisms Aid in the Removal and Addition of Proteins to the Ram Sperm Membrane. Proteomics 2020, 20, e1900289. [Google Scholar] [CrossRef]
- Gangnuss, S.; Sutton-McDowall, M.L.; Robertson, S.A.; Armstrong, D.T. Seminal plasma regulates corpora lutea macrophage populations during early pregnancy in mice. Biol. Reprod. 2004, 71, 1135–1141. [Google Scholar] [CrossRef] [Green Version]
- García-Rodríguez, A.; de la Casa, M.; Peinado, H.; Gosálvez, J.; Roy, R. Human prostasomes from normozoospermic and non-normozoospermic men show a differential protein expression pattern. Andrology 2018, 6, 585–596. [Google Scholar] [CrossRef] [Green Version]
- Murdica, V.; Cermisoni, G.C.; Zarovni, N.; Salonia, A.; Viganò, P.; Vago, R. Proteomic analysis reveals the negative modulator of sperm function glycodelin as over-represented in semen exosomes isolated from asthenozoospermic patients. Hum. Reprod. 2019, 34, 2314–2315. [Google Scholar] [CrossRef] [PubMed]
- Milardi, D.; Grande, G.; Vincenzoni, F.; Messana, I.; Ponecorvi, A.; De Marinis, L.; Castagnola, M.; Marana, R. Proteomic approach in the identification of fertility pattern in seminal plasma of fertile men. Fertil. Steril. 2012, 97, 67–73. [Google Scholar] [CrossRef] [PubMed]
- Lin, Y.; Liang, A.; He, Y.; Li, Z.; Li, Z.; Wang, G.; Sun, F. Proteomic analysis of seminal extracellular vesicle proteins involved in asthenozoospermia by iTRAQ. Mol. Reprod. Dev. 2019, 86, 1094–1105. [Google Scholar] [CrossRef] [PubMed]
- De Lazari, F.L.; Sontag, E.R.; Schneider, A.; Moura, A.A.A.; Vasconcelos, F.R.; Nagano, C.S.; Mattos, R.C.; Jobim, M.I.M.; Bustamante-Filho, I.C. Seminal plasma proteins and their relationship with sperm motility and morphology in boars. Andrologia 2019, 51, e13222. [Google Scholar] [CrossRef]
- Gilany, K.; Minai-Tehrani, A.; Savadi-Shiraz, E.; Rezadoost, H.; Lakpour, N. Exploring the human seminal plasma proteome: An unexplored gold mine of biomarker for male infertility and male reproduction disorder. J. Reprod. Infertil. 2015, 16, 61–71. [Google Scholar]
- Agarwal, A.; Durairajanayagam, D.; Halabi, J.; Peng, J.; Vazquez-Levin, M. Proteomics, oxidative stress and male infertility. Reprod. Biomed. Online 2014, 29, 32–58. [Google Scholar] [CrossRef] [Green Version]
- Park, K.H.; Kim, B.J.; Kang, J.; Nam, T.S.; Lim, J.M.; Kim, H.T.; Park, J.K.; Kim, Y.G.; Chae, S.W.; Kim, U.H. Ca2+ signaling tools acquired from prostasomes are required for progesterone-induced sperm motility. Sci. Signal. 2011, 4, ra31. [Google Scholar] [CrossRef]
- Bechoua, S.; Rieu, I.; Sion, B.; Grizard, G. Prostasomes as potential modulators of tyrosine phosphorylation in human spermatozoa. Syst. Biol. Reprod. Med. 2011, 57, 139–148. [Google Scholar] [CrossRef] [Green Version]
- Arienti, G.; Carlini, E.; Nicolucci, A.; Cosmi, E.V.; Santi, F.; Palmerini, C.A. The motility of human spermatozoa as influenced by prostasomes at various pH levels. Biol. Cell. 1999, 91, 51–54. [Google Scholar] [CrossRef]
- Vivacqua, A.; Siciliano, L.; Sabato, M.; Palma, A.; Carpino, A. Prostasomes as zinc ligands in human seminal plasma. Int. J. Androl. 2004, 27, 27–31. [Google Scholar] [CrossRef]
- Aalberts, M.; Sostaric, E.; Wubbolts, R.; Wauben, M.W.; Nolte-’t Hoen, E.N.; Gadella, B.M.; Stout, T.A.; Stoorvogel, W. Spermatozoa recruit prostasomes in response to capacitation induction. Biochim. Biophys. Acta 2013, 1834, 2326–2335. [Google Scholar] [CrossRef] [PubMed]
- Murdica, V.; Giacomini, E.; Alteri, A.; Bartolacci, A.; Cermisoni, G.C.; Zarovni, N.; Papaleo, E.; Montorsi, F.; Salonia, A.; Viganò, P.; et al. Seminal plasma of men with severe asthenozoospermia contain exosomes that affect spermatozoa motility and capacitation. Fertil. Steril. 2019, 111, 897–908. [Google Scholar] [CrossRef] [PubMed]
- Camargo, M.; Intasqui, P.; Bertolla, R.P. Understanding the seminal plasma proteome and its role in male fertility. Basic Clin. Androl. 2018, 28, 6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, Y.; Sun, Y.; Ni, A.; Shi, L.; Wang, P.; Isa, A.M.; Ge, P.; Jiang, L.; Fan, J.; Ma, H.; et al. Seminal Plasma Proteome as an Indicator of Sperm Dysfunction and Low Sperm Motility in Chickens. Mol. Cell Proteom. 2020, 19, 1035–1046. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Johnston, D.S.; Jelinsky, S.A.; Bang, H.J.; Dicandeloro, P.; Wilson, E.; Kopf, G.S.; Turner, T.T. The mouse epididymal transcriptome: Transcriptional profiling of segmental gene expression in the epididymis. Biol. Reprod. 2005, 73, 404–413. [Google Scholar] [CrossRef] [PubMed]
- Thimon, V.; Koukoui, O.; Calvo, E.; Sullivan, R. Region-specific gene expression profiling along the human epididymis. Mol. Hum. Reprod. 2007, 13, 691–704. [Google Scholar] [CrossRef]
- Zhou, W.; De Iuliis, G.N.; Dun, M.D.; Nixon, B. Characteristics of the epididymal luminal environment responsible for sperm maturation and storage. Front. Endocrinol. 2018, 9, 59. [Google Scholar] [CrossRef] [Green Version]
- Hermo, L.; Jacks, D. Nature’s ingenuity: Bypassing the classical secretory route via apocrine secretion. Mol. Reprod. Dev. 2002, 63, 394–410. [Google Scholar] [CrossRef]
- Dacheux, J.L.; Dacheux, F.; Druart, X. Epididymal protein markers and fertility. Anim. Reprod. Sci. 2016, 169, 76–87. [Google Scholar] [CrossRef]
- Yanagimachi, R.; Kamiguchi, Y.; Mikamo, K.; Suzuki, F.; Yanagimachi, H. Maturation of spermatozoa in the epididymis of the Chinese hamster. Am. J. Anat. 1985, 172, 317–330. [Google Scholar] [CrossRef]
- Dott, H.M.; Dingle, J.T. Distribution of lysosomal enzymes in the spermatozoa and cytoplasmic droplets of bull and ram. Exp. Cell Res. 1968, 52, 523–540. [Google Scholar] [CrossRef]
- Jones, S.; Lukanowska, M.; Suhorutsenko, J.; Oxenham, S.; Barratt, C.; Publicover, S.; Copolovici, D.M.; Langel, Ü.; Howl, J. Intracellular translocation and differential accumulation of cell-penetrating peptides in bovine spermatozoa: Evaluation of efficient delivery vectors that do not compromise human sperm motility. Hum. Reprod. 2013, 28, 1874–1889. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Girouard, J.; Frenette, G.; Sullivan, R. Comparative proteome and lipid profiles of bovine epididymosomes collected in the intraluminal compartment of the caput and cauda epididymidis. Int. J. Androl. 2011, 34, e475–e486. [Google Scholar] [CrossRef] [PubMed]
- Nixon, B.; De Iuliis, G.N.; Hart, H.M.; Zhou, W.; Mathe, A.; Bernstein, I.R.; Anderson, A.L.; Stanger, S.J.; Skerrett-Byrne, D.A.; Jamaluddin, M.F.; et al. Proteomic profiling of mouse epididymosomes reveals their contributions to post-testicular sperm maturation. Mol. Cell. Proteom. 2019, 18, S91–S108. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frenette, G.; Girouard, J.; D’Amours, O.; Allard, N.; Tessier, L.; Sullivan, R. Characterization of two distinct populations of epididymosomes collected in the intraluminal compartment of the bovine cauda epididymis. Biol. Reprod. 2010, 83, 473–480. [Google Scholar] [CrossRef] [Green Version]
- Simon, C.; Greening, D.W.; Bolumar, D.; Balaguer, N.; Salamonsen, L.A.; Vilella, F. Extracellular Vesicles in Human Reproduction in Health and Disease. Endocr. Rev. 2018, 39, 292–332. [Google Scholar] [CrossRef] [Green Version]
- D’Amours, O.; Frenette, G.; Bordeleau, L.J.; Allard, N.; Leclerc, P.; Blondin, P.; Sullivan, R. Epididymosomes transfer epididymal sperm binding protein 1 (ELSPBP1) to dead spermatozoa during epididymal transit in bovine. Biol. Reprod. 2012, 87, 94. [Google Scholar] [CrossRef]
- Sutovsky, P.; Moreno, R.; Ramalho-Santos, J.; Dominko, T.; Thompson, W.E.; Schatten, G. A putative, ubiquitin-dependent mechanism for the recognition and elimination of defective spermatozoa in the mammalian epididymis. J. Cell Sci. 2001, 114, 1665–1675. [Google Scholar]
- Cooper, T.G. Interactions between epididymal secretions and spermatozoa. J. Reprod. Fertil. Suppl. 1998, 53, 119–136. [Google Scholar]
- Sengupta, P.; Baird, B.; Holowka, D. Lipid rafts, fluid/fluid phase separation, and their relevance to plasma membrane structure and function. Semin. Cell Dev. Biol. 2007, 18, 583–590. [Google Scholar] [CrossRef] [Green Version]
- Girouard, J.; Frenette, G.; Sullivan, R. Compartmentalization of proteins in epididymosomes coordinates the association of epididymal proteins with the different functional structures of bovine spermatozoa. Biol. Reprod. 2009, 80, 965–972. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frenette, G.; Lessard, C.; Sullivan, R. Selected proteins of “prostasome-like particles” from epididymal cauda fluid are transferred to epididymal caput spermatozoa in bull. Biol. Reprod. 2002, 67, 308–313. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shum, W.W.; Ruan, Y.C.; Da Silva, N.; Breton, S. Establishment of cell-cell cross talk in the epididymis: Control of luminal acidification. J. Androl. 2011, 32, 576–586. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bedford, J.M. Changes in the electrophoretic properties of rabbit spermatozoa during passage through the epididymis. Nature 1963, 200, 1178–1180. [Google Scholar] [CrossRef] [PubMed]
- Björkgren, I.; Sipilä, P. The impact of epididymal proteins on sperm function. Reproduction 2019, 158, R155–R167. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hu, J.; Merriner, D.J.; O’Connor, A.E.; Houston, B.J.; Furic, L.; Hedger, M.P.; O’Bryan, M.K. Epididymal cysteine-rich secretory proteins are required for epididymal sperm maturation and optimal sperm function. Mol. Hum. Reprod. 2018, 24, 111–122. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin-DeLeon, P.A. Epididymal SPAM1 and its impact on sperm function. Mol. Cell. Endocrinol. 2006, 250, 114–121. [Google Scholar] [CrossRef]
- Eickhoff, R.; Baldauf, C.; Koyro, H.W.; Wennemuth, G.; Jürgen Seitz, Y.S.; Henkel, R.; Meinhardt, A. Influence of macrophage migration inhibitory factor (MIF) on the zinc content and redox state of protein-bound sulphydryl groups in rat sperm: Indications for a new role of MIF in sperm maturation. Mol. Hum. Reprod. 2004, 10, 605–611. [Google Scholar] [CrossRef] [Green Version]
- Chabory, E.; Damon, C.; Lenoir, A.; Kauselmann, G.; Kern, H.; Zevnik, B.; Garrel, C.; Saez, F.; Cadet, R.; Henry-Berger, J.; et al. Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice. J. Clin. Investig. 2009, 119, 2074–2085. [Google Scholar] [CrossRef]
- Vyas, P.; Balakier, H.; Librach, C.L. Ultrastructural identification of CD9 positive extracellular vesicles released from human embryos and transported through the zona pellucida. Syst. Biol. Reprod. Med. 2019, 65, 273–280. [Google Scholar] [CrossRef] [Green Version]
- Nixon, B.; MacIntyre, D.A.; Mitchell, L.A.; Gibbs, G.M.; O’Bryan, M.; Aitken, R.J. The identification of mouse sperm-surface-associated proteins and characterization of their ability to act as decapacitation factors. Biol. Reprod. 2006, 74, 275–287. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Szczykutowicz, J.; Kałuża, A.; Kaźmierowska-Niemczuk, M.; Ferens-Sieczkowska, M. The Potential Role of Seminal Plasma in the Fertilization Outcomes. Biomed. Res Int. 2019, 2019, 5397804. [Google Scholar] [CrossRef] [PubMed]
- Ronquist, G.; Hedstrom, M. Restoration of detergent-inactivated adenosine triphosphatase activity of human prostatic fluid with concanavalin A. Biochim. Biophys. Acta 1977, 483, 483–486. [Google Scholar] [CrossRef]
- Arienti, G.; Carlini, E.; Polci, A.; Cosmi, E.V.; Palmerini, C.A. Fatty acid pattern of human prostasome lipid. Arch. Biochem. Biophys. 1998, 358, 391–395. [Google Scholar] [CrossRef]
- Aalberts, M.; van Dissel-Emiliani, F.M.; van Adrichem, N.P.; van Wijnen, M.; Wauben, M.H.; Stout, T.A.; Stoorvogel, W. Identification of distinct populations of prostasomes that differentially express prostate stem cell antigen, annexin A1, and GLIPR2 in humans. Biol. Reprod. 2012, 86, 82. [Google Scholar] [CrossRef]
- Utleg, A.G.; Yi, E.C.; Xie, T.; Shannon, P.; White, J.T.; Goodlett, D.R.; Hood, L.; Lin, B. Proteomic analysis of human prostasomes. Prostate 2003, 56, 150–161. [Google Scholar] [CrossRef]
- Poliakov, A.; Spilman, M.; Dokland, T.; Amling, C.L.; Mobley, J.A. Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen. Prostate 2009, 69, 159–167. [Google Scholar] [CrossRef]
- Ronquist, G. Prostasomes: Their Characterisation: Implications for Human Reproduction: Prostasomes and Human Reproduction. Adv. Exp. Med. Biol. 2015, 868, 191–209. [Google Scholar]
- Ronquist, K.G.; Ek, B.; Morrell, J.; Stavreus-Evers, A.; Ström Holst, B.; Humblot, P.; Ronquist, G.; Larsson, A. Prostasomes from four different species are able to produce extracellular adenosine triphosphate (ATP). Biochim. Biophys. Acta 2013, 1830, 4604–4610. [Google Scholar] [CrossRef] [Green Version]
- Stegmayr, B.; Ronquist, G. Promotive effect on human sperm progressive motility by prostasomes. Urol. Res. 1982, 10, 253–257. [Google Scholar] [CrossRef]
- Palmerini, C.; Saccardi, C.; Carlini, E.; Fabiani, R.; Arienti, G. Fusion of prostasomes to human spermatozoa stimulates the acrosome reaction. Fertil. Steril. 2003, 80, 1181–1184. [Google Scholar] [CrossRef]
- Arienti, G.; Carlini, E.; Palmerini, C.A. Fusion of human sperm to prostasomes at acidic pH. J. Membr. Biol. 1997, 155, 89–94. [Google Scholar] [CrossRef] [PubMed]
- Skibinski, G.; Kelly, R.W.; Harkiss, D.; James, K. Immunosuppression by human seminal plasma--extracellular organelles (prostasomes) modulate activity of phagocytic cells. Am. J. Reprod. Immunol. 1992, 28, 97–103. [Google Scholar] [CrossRef] [PubMed]
- Vickram, A.S.; Samad, H.A.; Latheef, S.K.; Chakraborty, S.; Dhama, K.; Sridharan, T.B.; Sundaram, T.; Gulothungan, G. Human prostasomes an extracellular vesicle—Biomarkers for male infertility and prostate cancer: The journey from identification to current knowledge. Int. J. Biol. Macromol. 2020, 146, 946–958. [Google Scholar] [CrossRef] [PubMed]
- Bailey, J.L. Factors regulating sperm capacitation. Syst. Biol. Reprod. Med. 2010, 56, 334–348. [Google Scholar] [CrossRef]
- Flesch, F.M.; Brouwers, J.F.; Nievelstein, P.F.; Verkleij, A.J.; van Golde, L.M.; Colenbrander, B.; Gadella, B.M. Bicarbonate stimulated phospholipid scrambling induces cholesterol redistribution and enables cholesterol depletion in the sperm plasma membrane. J. Cell Sci. 2001, 114, 3543–3555. [Google Scholar]
- Visconti, P.E.; Westbrook, V.A.; Chertihin, O.; Demarco, I.; Sleight, S.; Diekman, A.B. Novel signaling pathways involved in sperm acquisition of fertilizing capacity. J. Reprod. Immunol. 2002, 53, 133–150. [Google Scholar] [CrossRef]
- Puga Molina, L.C.; Pinto, N.A.; Torres, N.I.; González-Cota, A.L.; Luque, G.M.; Balestrini, P.A.; Romarowski, A.; Krapf, D.; Santi, C.M.; Treviño, C.L.; et al. CFTR/ENaC-dependent regulation of membrane potential during human sperm capacitation is initiated by bicarbonate uptake through NBC. J. Biol. Chem. 2018, 293, 9924–9936. [Google Scholar] [CrossRef] [Green Version]
- Candenas, L.; Pinto, F.M.; Cejudo-Román, A.; González-Ravina, C.; Fernández-Sánchez, M.; Irazusta, J.; Pérez-Hernández, N.; Subirán, N. Veratridine-sensitive Na+ channels regulate human sperm fertilization capacity. Life Sci. 2018, 196, 48–55. [Google Scholar] [CrossRef]
- Pons-Rejraji, H.; Artonne, C.; Sion, B.; Brugnon, F.; Canis, M.; Janny, L.; Grizard, G. Prostasomes: Inhibitors of capacitation and modulators of cellular signalling in human sperm. Int. J. Androl. 2011, 34, 568–580. [Google Scholar] [CrossRef]
- Publicover, S.; Harper, C.V.; Barratt, C. [Ca2+]i signalling in sperm—Making the most of what you’ve got. Nat. Cell Biol. 2007, 9, 235–242. [Google Scholar] [CrossRef] [PubMed]
- Jin, M.; Fujiwara, E.; Kakiuchi, Y.; Okabe, M.; Satouh, Y.; Baba, S.A.; Chiba, K.; Hirohashi, N. Most fertilizing mouse spermatozoa begin their acrosome reaction before contact with the zona pellucida during in vitro fertilization. Proc. Natl. Acad. Sci. USA 2011, 108, 4892–4896. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Agarwal, A.; Majzoub, A.; Parekh, N.; Henkel, R. A Schematic Overview of the Current Status of Male Infertility Practice. World J. Men’s Health 2019, 38, 308. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pilch, B.; Mann, M. Large-scale and high-confidence proteomic analysis of human seminal plasma. Gen. Biol. 2006, 7, R40. [Google Scholar] [CrossRef] [Green Version]
- Agarwal, A.; Ayaz, A.; Samanta, L.; Sharma, R.; Assidi, M.; Abuzenadah, A.M.; Sabanegh, E. Comparative proteomic network signatures in seminal plasma of infertile men as a function of reactive oxygen species. Clin. Proteom. 2015, 12, 23. [Google Scholar] [CrossRef] [Green Version]
- Yang, C.; Guo, W.B.; Zhang, W.S.; Bian, J.; Yang, J.K.; Zhou, Q.Z.; Chen, M.K.; Peng, W.; Qi, T.; Wang, C.Y.; et al. Comprehensive proteomics analysis of exosomes derived from human seminal plasma. Andrology 2017, 5, 1007–1015. [Google Scholar] [CrossRef] [Green Version]
- Wu, Y.; Yuan, Y.; Chen, L.; Wang, M.; Yang, Y.; Wang, Y.; Quan, C.; Chen, D.; Chen, Y.; Huang, X.; et al. Quantitative Proteomic Analysis of Human Seminal Plasma from Normozoospermic and Asthenozoospermic Individuals. Biomed. Res. Int. 2019, 2019, 2735038. [Google Scholar] [CrossRef] [Green Version]
- De Lamirande, E. Semenogelin, the main protein of the human semen coagulum, regulates sperm function. Semin. Thromb. Hemost. 2007, 33, 60–68. [Google Scholar] [CrossRef]
- Herwig, R.; Knoll, C.; Planyavsky, M.; Pourbiabany, A.; Greilberger, J.; Bennett, K.L. Proteomic analysis of seminal plasma from infertile patients with oligoasthenoteratozoospermia due to oxidative stress and comparison with fertile volunteers. Fertil. Steril. 2013, 100, 355–366. [Google Scholar] [CrossRef]
- Dias, T.R.; Samanta, L.; Agarwal, A.; Pushparaj, P.N.; Panner Selvam, M.K.; Sharma, R. Proteomic Signatures Reveal Differences in Stress Response, Antioxidant Defense and Proteasomal Activity in Fertile Men with High Seminal ROS Levels. Int. J. Mol. Sci. 2019, 20, 203. [Google Scholar] [CrossRef] [Green Version]
- Druart, X.; Rickard, J.P.; Tsikis, G.; de Graaf, S.P. Seminal plasma proteins as markers of sperm fertility. Theriogenology 2019, 137, 30–35. [Google Scholar] [CrossRef] [PubMed]
- Gonzales, G.F. Function of seminal vesicles and their role on male fertility. Asian J. Androl. 2001, 3, 251–258. [Google Scholar] [PubMed]
- Elzanaty, S.; Erenpreiss, J.; Becker, C. Seminal plasma albumin: Origin and relation to the male reproductive parameters. Andrologia 2007, 39, 60–65. [Google Scholar] [CrossRef] [PubMed]
- Drake, R.R.; White, K.Y.; Fuller, T.W.; Igwe, E.; Clements, M.A.; Nyalwidhe, J.O.; Given, R.W.; Lance, R.S.; Semmes, O.J. Clinical collection and protein properties of expressed prostatic secretions as a source for biomarkers of prostatic disease. J. Proteom. 2009, 72, 907–917. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rao, A.R.; Motiwala, H.G.; Karim, O.M. The discovery of prostate-specific antigen. BJU Int. 2008, 101, 5–10. [Google Scholar] [CrossRef] [PubMed]
- Kirchhoff, C. Molecular characterization of epididymal proteins. Rev. Reprod. 1998, 3, 86–95. [Google Scholar] [CrossRef]
- Thimon, V.; Frenette, G.; Saez, F.; Thabet, M.; Sullivan, R. Protein composition of human epididymosomes collected during surgical vasectomy reversal: A proteomic and genomic approach. Hum. Reprod. 2008, 23, 1698–1707. [Google Scholar] [CrossRef] [Green Version]
- Rolland, A.D.; Lavigne, R.; Dauly, C.; Calvel, P.; Kervarrec, C.; Freour, T.; Evrard, B.; Rioux-Leclercq, N.; Auger, J.; Pineau, C. Identification of genital tract markers in the human seminal plasma using an integrative genomics approach. Hum. Reprod. 2013, 28, 199–209. [Google Scholar] [CrossRef] [Green Version]
- Evans, E.A.; Zhang, H.; Martin-DeLeon, P.A. SPAM1 (PH-20) protein and mRNA expression in the epididymides of humans and macaques: Utilizing laser microdissection/RT-PCR. Reprod. Biol. Endocrinol. 2003, 1, 54. [Google Scholar] [CrossRef] [Green Version]
- Batruch, I.; Lecker, I.; Kagedan, D.; Smith, C.R.; Mullen, J.; Grober, E.; Lo, K.C.; Diamandis, E.P.; Jarvi, K.A. 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, 941–953. [Google Scholar] [CrossRef]
- Davalieva, K.; Kiprijanovska, S.; Noveski, P.; Plaseski, T.; Kocevska, B.; Plaseska-Karanfilska, D. Human seminal plasma proteome study: A search for male infertility biomarkers. Balkan J. Med. Genet. 2012, 15, 35–38. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mann, T. Protein constituents and enzymes of the seminal plasma. In The Biochemistry of Semen and of the Male Reproductive Tract, 2nd ed.; Methuen: London, UK, 1964; pp. 161–192. [Google Scholar]
- Edwards, J.J.; Tollaksen, S.L.; Anderson, N.G. Proteins of human semen. I. Two-dimensional mapping of human seminal fluid. Clin. Chem. 1981, 27, 1335–1340. [Google Scholar] [CrossRef] [PubMed]
- Ayyagari, R.R.; Fazleabas, A.T.; Dawood, M.Y. Seminal plasma proteins of fertile and infertile men analyzed by two-dimensional electrophoresis. Am. J. Obstet. Gynecol. 1987, 157, 1528–1533. [Google Scholar] [CrossRef]
- Starita-Geribaldi, M.; Poggioli, S.; Zucchini, M.; Garin, J.; Chevallier, D.; Fenichel, P.; Pointis, G. Mapping of seminal plasma proteins by two-dimensional gel electrophoresis in men with normal and impaired spermatogenesis. Mol. Hum. Reprod. 2001, 7, 715–722. [Google Scholar] [CrossRef]
- Batruch, I.; Smith, C.R.; Mullen, B.J.; Grober, E.; Lo, K.C.; Diamandis, E.P.; Jarvi, K.A. Analysis of seminal plasma from patients with non-obstructive azoospermia and identification of candidate biomarkers of male infertility. J. Proteome Res. 2012, 11, 1503–1511. [Google Scholar] [CrossRef]
- Subiran, N.; Agirregoitia, E.; Valdivia, A.; Ochoa, C.; Casis, L.; Irazusta, J. Expression of enkephalin-degrading enzymes in human semen and implications for sperm motility. Fertil. Steril. 2008, 89, 1571–1577. [Google Scholar] [CrossRef]
- Pinto, F.M.; Ravina, C.G.; Subiran, N.; Cejudo-Román, A.; Fernández-Sánchez, M.; Irazusta, J.; Garrido, N.; Candenas, L. Autocrine regulation of human sperm motility by tachykinins. Reprod. Biol. Endocrinol. 2010, 8, 104. [Google Scholar] [CrossRef] [Green Version]
- Sharma, R.; Agarwal, A.; Mohanty, G.; Du Plessis, S.S.; Gopalan, B.; Willard, B.; Satya, P.; Yadav, S.P.; Edmund Sabanegh, E. Proteomic analysis of seminal fluid from men exhibiting oxidative stress. Reprod. Biol. Endocrinol. 2013, 11, 85. [Google Scholar] [CrossRef] [Green Version]
- Panner Selvam, M.K.; Agarwal, A.; Baskaran, S. Proteomic analysis of seminal plasma from bilateral varicocele patients indicates an oxidative state and increased inflammatory response. Asian J. Androl. 2019, 21, 544–550. [Google Scholar]
- Fariello, R.M.; Pariz, J.R.; Spaine, D.M.; Gozzo, F.C.; Pilau, E.J.; Fraietta, R.; Bertolla, R.P.; Andreoni, C.; Cedenho, A.P. Effect of smoking on the functional aspects of sperm and seminal plasma protein profiles in patients with varicocele. Hum. Reprod. 2012, 27, 3140–3149. [Google Scholar] [CrossRef] [Green Version]
- Martins, A.D.; Panner Selvam, M.K.; Agarwal, A.; Alves, M.G.; Baskaran, S. Alterations in seminal plasma proteomic profile in men with primary and secondary infertility. Sci. Rep. 2020, 10, 7539. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Wang, W.; Zhu, P.; Wang, J.; Wang, Y.; Wang, X.; Liu, J.; Li, N.; Wang, X.; Lin, C.; et al. In-depth quantitative proteome analysis of seminal plasma from men with oligoasthenozoospermia and normozoospermia. Reprod. Biomed. Online 2018, 37, 467–479. [Google Scholar] [CrossRef]
- Starita-Geribaldi, M.; Roux, F.; Garin, J.; Chevallier, D.; Fénichel, P.; Pointis, G. Development of narrow immobilized pH gradients covering one pH unit for human seminal plasma proteomic analysis. Proteomics 2003, 3, 1611–1619. [Google Scholar] [CrossRef]
- Sharma, R.; Agarwal, A.; Mohanty, G.; Jesudasan, R.; Gopalan, B.; Willard, B.; Satya, P.; Yada, S.P.; Sabanegh, E. Functional proteomic analysis of seminal plasma proteins in men with various semen parameters. Reprod. Biol. Endocrinol. 2013, 11, 38. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Légaré, C.; Cloutier, F.; Makosso-Kallyth, S.; Laflamme, L.; Jarvi, K.; Tremblay, R.R.; Sullivan, R. Cysteine-rich secretory protein 1 in seminal plasma: Potential biomarker for the distinction between obstructive and nonobstructive azoospermia. Fertil. Steril. 2013, 100, 1253–1260. [Google Scholar] [CrossRef] [PubMed]
- Del Giudice, P.T.; Belardin, L.B.; Camargo, M.; Zylbersztejn, D.S.; Carvalho, V.M.; Cardozo, K.H.M.; Bertolla, R.P.; Cedenho, A.P. Determination of testicular function in adolescents with varicocoele—A proteomics approach. Andrology 2016, 4, 447–455. [Google Scholar] [CrossRef]
- Zylbersztejn, D.S.; Andreoni, C.; Del Giudice, P.T.; Montagnini Spaine, D.; Borsari, L.; Souza, G.H.M.F.; Bertolla, R.P.; Fraietta, R. Proteomic analysis of seminal plasma in adolescents with and without varicocele. Fertil. Steril. 2013, 99, 92–98. [Google Scholar] [CrossRef]
- Belardin, L.B.; Del Giudice, P.T.; Camargo, M.; Intasqui, P.; Antoniassi, M.P.; Bertolla, R.P.; Cedenho, A.P. Alterations in the proliferative/apoptotic equilibrium in semen of adolescents with varicocele. J. Assist. Reprod. Genet. 2016, 33, 1657–1664. [Google Scholar] [CrossRef] [PubMed]
- Yamakawa, K.; Yoshida, K.; Nishikawa, H.; Kato, T.; Iwamoto, T. Comparative analysis of interindividual variations in the seminal plasma proteome of fertile men with identification of potential markers for azoospermia in infertile patients. J. Androl. 2007, 28, 858–865. [Google Scholar] [CrossRef]
- Giacomini, E.; Ura, B.; Giolo, E.; Luppi, S.; Martinelli, M.; Garcia, R.C.; Ricci, G. Comparative analysis of the seminal plasma proteomes of oligoasthenozoospermic and normozoospermic men. Reprod. Biomed. Online 2015, 30, 522–531. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Drabovich, A.P.; Dimitromanolakis, A.; Saraon, P.; Soosaipillai, A.; Batruch, I.; Mullen, B.; Jarvi, K.; Diamandis, E.P. Differential diagnosis of azoospermia with proteomic biomarkers ECM1 and TEX101 quantified in seminal plasma. Sci. Transl. Med. 2013, 5, 212ra160. [Google Scholar] [CrossRef]
- Intasqui, P.; Agarwal, A.; Sharma, R.; Samanta, L.; Bertolla, R.P. Towards the identification of reliable sperm biomarkers for male infertility: A sperm proteomic approach. Andrologia 2018, 50, 10. [Google Scholar] [CrossRef] [PubMed]
- Panner Selvam, M.K.; Agarwal, A. Proteomic profiling of seminal plasma proteins in varicocele patients. World J. Men’s Health 2019, 37, e12. [Google Scholar] [CrossRef] [PubMed]
- Diamandis, E.P.; Arnett, W.P.; Foussias, G.; Pappas, H.; Ghandi, S.; Melegos, D.N.; Mullen, B.; Yu, H.; Srigley, J.; Jarvi, K. Seminal plasma biochemical markers and their association with semen analysis findings. Urology 1999, 53, 596–603. [Google Scholar] [CrossRef]
- Heshmat, S.M.; Mullen, J.B.; Jarvi, K.A.; Soosaipillai, A.; Diamandis, E.P.; Hamilton, R.J.; Lo, K.C. Seminal plasma lipocalin-type prostaglandin D synthase: A potential new marker for the diagnosis of obstructive azoospermia. J. Urol. 2008, 179, 1077–1080. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Wang, J.; Zhang, H.R.; Shi, H.J.; Ma, D.; Zhao, H.-X.; Lin, B.; Li, R.S. Proteomic analysis of seminal plasma from asthenozoospermia patients reveals proteins that affect oxidative stress responses and semen quality. Asian J. Androl. 2009, 11, 484–491. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ballescá, J.L.; Balasch, J.; Calafell, J.M.; Alvarez, R.; Fábregues, F.; de Osaba, M.J.; Ascaso, C.; Vanrell, J.A. Serum inhibin B determination is predictive of successful testicular sperm extraction in men with non-obstructive azoospermia. Hum. Reprod. 2000, 15, 1734–1738. [Google Scholar]
- Fénichel, P.; Rey, R.; Poggioli, S.; Donzeau, M.; Chevallier, D.; Pointis, G. Anti-Müllerian hormone as a seminal marker for spermatogenesis in non-obstructive azoospermia. Hum. Reprod. 1999, 14, 2020–2024. [Google Scholar] [CrossRef] [Green Version]
- Andersen, J.M.; Herning, H.; Witczak, O.; Haugen, T.B. Anti-Müllerian hormone in seminal plasma and serum: Association with sperm count and sperm motility. Hum. Reprod. 2016, 31, 1662–1667. [Google Scholar] [CrossRef] [Green Version]
- Nery, S.F.; Vieira, M.A.; Dela Cruz, C.; Lobach, V.N.M.; Del Puerto, H.L.; Torres, P.B.; Rocha, A.L.L.; Reis, A.B.; Reis, F.M. Seminal plasma concentrations of Anti-Müllerian hormone and inhibin B predict motile sperm recovery from cryopreserved semen in asthenozoospermic men: A prospective cohort study. Andrology 2014, 2, 918–923. [Google Scholar] [CrossRef]
- Chiu, W.W.; Chamley, L.W. Human seminal plasma prolactin-inducible protein is an immunoglobulin G-binding protein. J. Reprod. Immunol. 2003, 60, 97–111. [Google Scholar] [CrossRef]
- World Health Organization (WHO). WHO Laboratory Manual for the Examination and Processing of Human Semen, 5th ed.; Cambridge University Press: New York, NY, USA, 2010. [Google Scholar]
- Agarwal, A.; Sharma, R.K.; Nallella, K.P.; Thomas, A.J., Jr.; Alvarez, J.G.; Sikka, S.C. Reactive oxygen species as an independent marker of male factor infertility. Fertil. Steril. 2006, 86, 878–885. [Google Scholar] [CrossRef] [PubMed]
- Bracke, A.; Peeters, K.; Punjabi, U.; Hoogewijs, D.; Dewilde, S. A search for molecular mechanisms underlying male idiopathic infertility. Reprod. Biomed. Online 2018, 36, 327–339. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Intasqui, P.; Camargo, M.; Antoniassi, M.P.; Cedenho, A.P.; Carvalho, V.M.; Cardozo, K.H.M.; Zylbersztejn, D.S.; Bertolla, R.P. Association between the seminal plasma proteome and sperm functional traits. Fertil. Steril. 2016, 105, 617–628. [Google Scholar] [CrossRef]
- 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. Proteome Res. 2014, 13, 5403–5414. [Google Scholar] [CrossRef] [PubMed]
- González-Ravina, C.; Aguirre-Lipperheide, M.; Pinto, F.; Martín-Lozano, D.; Fernández-Sánchez, M.; Blasco, V.; Santamaría-López, E.; Candenas, L. Effect of dietary supplementation with a highly pure and concentrated docosahexaenoic acid (DHA) supplement on human sperm function. Reprod. Biol. 2018, 18, 282–288. [Google Scholar] [CrossRef]
- Intasqui, P.; Antoniassi, M.P.; Camargo, M.; Nichi, M.; Carvalho, V.M.; Cardozo, K.H.; Zylbersztejn, D.S.; Bertolla, R.P. Differences in the seminal plasma proteome are associated with oxidative stress levels in men with normal semen parameters. Fertil. Steril. 2015, 104, 292–301. [Google Scholar] [CrossRef]
- Blobel, C.P.; Wolfsberg, T.G.; Turck, C.W.; Myles, D.G.; Primakoff, P.; White, J.M. A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature 1992, 356, 248–252. [Google Scholar] [CrossRef]
- Fernandez, D.; Valdivia, A.; Irazusta, J.; Ochoa, C.; Casis, L. Peptidase activities in human semen. Peptides 2002, 23, 461–468. [Google Scholar] [CrossRef]
- Panner Selvam, M.K.; Agarwal, A. Sperm and Seminal Plasma Proteomics: Molecular Changes Associated with Varicocele-Mediated Male Infertility. World J. Men’s Health 2019, 37, e43. [Google Scholar] [CrossRef] [Green Version]
- Agarwal, A.; Sharma, R.; Harlev, A.; Esteves, S.C. Effect of varicocele on semen characteristics according to the new 2010 World Health Organization criteria: A systematic review and meta-analysis. Asian J. Androl. 2016, 18, 163–170. [Google Scholar] [CrossRef] [PubMed]
- Panner Selvam, M.K.; Agarwa, A.; Sharma, R.; Samanta, L.; Gupta, S.; Dias, T.R.; Martins, A.D. Protein Fingerprinting of Seminal Plasma Reveals Dysregulation of Exosome-Associated Proteins in Infertile Men with Unilateral Varicocele. World J. Men’s Health 2019, 37, e18. [Google Scholar] [CrossRef] [PubMed]
- Munuce, M.J.; Marini, P.E.; Teijeiro, J.M. Expression profile and distribution of Annexin A1, A2 and A5 in human semen. Andrologia 2019, 51, e13224. [Google Scholar] [CrossRef] [PubMed]
- Cescon, M.; Chianese, R.; Tavares, R.S. Environmental impact on male (In)fertility via epigenetic route. J. Clin. Med. 2020, 9, 2520. [Google Scholar] [CrossRef] [PubMed]
Protein | Infertility Relationship | References |
---|---|---|
Albumin preprotein (ALB precursor) | Exclusively expressed in patients with high levels of ROS | [111] |
Aldose reductase (ALDR) | Increased in patients with oliagoasthenoteratozoospermia and high levels of ROS | [111] |
Highly increased in bilateral varicocele | [112] | |
Alpha-1-acid glycoprotein 1 (ORM1), | Highly decreased in bilateral varicocele | [112] |
Alpha-1-acid glycoprotein 2 (ORM2) | Highly decreased in bilateral varicocele | [112] |
α-1-antichymotrypsin (AACT) | Increased in patients with oliagoasthenoteratozoospermia and high levels of ROS | [111] |
α -1-antitrypsin (SERPINA1) | Highly decreased in bilateral varicocele | [112] |
Absent in varicocele | [113] | |
Apolipoprotein D (APOD) | Highly decreased in bilateral varicocele | [112] |
Annexin 2 (ANXA2) | Increased in primary infertility | [114] |
Decreased in asthenozoospermia | [89] | |
ATP synthase subunit alpha (ATP5A1). | Decreased in oligoasthenozoospermia | [115] |
Cathepsin L1 (CTSL) | Increased in oligoasthenozoospermia | [115] |
CDC42 | Increased in primary infertility | [114] |
Clusterin (CLU) | Highly decreased in azoospermia | [116] |
Decreased in oligozoospermia | [117] | |
Cysteine-rich secretory protein 1 (CRISP1) | Highly decreased or absent in OA | [116,118] |
Decreased in oligoasthenozoospermia | [115] | |
Decreased in dyspermia | [22] | |
Decreased in asthenozoospermia | [23,34] | |
Absent in varicocele | [113] | |
Cysteine-rich secretory protein 3 (CRISP3) | Increased in varicocele | [119] |
Deoxyribonuclease-1 (DNase I) | Decreased in varicocele | [119,120,121] |
Dipeptidase 3 (DPEP3) | Expressed exclusively in fertile controls | [102,108] |
Diacylglycerol kinase eta (DGK) | Increased in patients with oliagoasthenoteratozoospermia and high levels of ROS | [111] |
Epididymal secretory protein E1 (NPC2) | Highly decreased or absent in azoospermia | [116] |
Absent in OA | [122] | |
Decreased in oligoasthenozoospermia | [115,123] | |
Absent in varicocele | [120] | |
Epididymal secretory protein E3-alpha (EDDM3A) | Highly increased in asthenozoospermia | [23] |
Epididymal sperm-binding protein 1 (ELSPBP1) | Decreased in oligoasthenozoospermia | [115] |
Decreased in dyspermia | [22] | |
Extracellular matrix protein 1 (ECM1) | Decreased in oligoasthenozoospermia | [115] |
Highly increased in bilateral varicocele | [112] | |
ECM1 and Testis-expressed sequence 101 (TEX101) | Diagnosis and differentiation of OA and NOA. Differentiation of NOA subtypes | [10,124] |
Family with sequence similarity 3 (FAM3D) | Absent in patients with high levels of ROS | [87] |
Fatty acid synthase (FASN) | Highly increased in bilateral varicocele | [112] |
Fibromodulin (FMOD) | Decreased in oligoasthenozoospermia | [115] |
Fibronectin (FN1) | Increased in azoospermia | [103] |
Highly increased in bilateral varicocele | [112] | |
Fibronectin I isoform 3 preprotein/fibronectin 1 isoform b precursor (FN1 precursor) | Absent in patients with high levels of ROS | [111] |
Galectin-3 binding protein (LGALS3BP) | Decreased in oligozoospermia | [117] |
Decreased in oligoasthenozoospermia | [123] | |
Increased in azoospermia | [103] | |
Absent in patients with high levels of ROS | [111] | |
Glutathione hydrolase 1 proenzyme (GGT1) | Highly decreased in bilateral varicocele | [112] |
Gammaglutamyltransferase 7 (GGT7) | Expressed exclusively in NOA | [108] |
Glutathione S-transferase P (GSTP1) | Increased in oligoasthenozoospermia | [115] |
Glycodelin (PAEP) | Highly increased in oligoasthenozoospermia | [115] |
Highly increased in asthenozoospermia | [23] | |
Heat shock-related 70 kDa protein 2 (HSP72) | Increased in asthenozoospermia | [89] |
Histone H2B type 1-A (HIST1H2BA) | Expressed exclusively in fertile controls | [102,108,125] |
Increased in dyspermia | [22] | |
Insulin-like growth factor binding protein-3 (IGFBP-3) | Expressed exclusively in clinical varicocele | [120] |
Insulin-like growth factor-binding protein 7 (IGFBP7) | Increased in varicocele | [119,121] |
Kallikrein-2 (KLK2) | Decreased in dyspermia | [22] |
Decreased in asthenozoospermia | [89] | |
L-lactate dehydrogenase C chain (LDHC) | Expressed exclusively in fertile controls | [100,102,108] |
Highly decreased in asthenozoospermia | [89] | |
Decreased in dyspermia | [22] | |
Lactotransferrin (LTF) | Increased in teratozoospermia | [117] |
Increased in oligoasthenozoospermia | [115] | |
Lactotransferrin precursor-1 peptide (LTF precursor) | Exclusively expressed in patients with high levels of ROS | [111] |
Lipocalin-1 (LCN-1) | Increased in oligoasthenozoospermia | [123] |
Macrophage migration inhibitory factor (MIF) | Decreased in dyspermia | [22] |
Absent in patients with high levels of ROS | [111] | |
Membrane metallo-endopeptidase (MME) | Highly increased in patients with high levels of ROS | [87] |
N-acetylglucosamine-1-phosphotransferase subunit gamma (GNPTG) | Increased in oligoasthenozoospermia | [115] |
Orosomucoid 1 precursor (ORM1) | Decreased in teratozoospermia | [117] |
Peroxiredoxin-1 (PRDX1) | Increased in varicocele | [126] |
Peroxiredoxin-2 (PRDX2) | Increased in varicocele | [126] |
Highly increased in bilateral varicocele | [112] | |
Phosphoglycerate kinase 2 (PGK2) | Expressed exclusively in fertile controls | [100,102,108] |
Decreased in varicocele | [126] | |
Polymeric immunoglobulin receptor (PIGR) | Highly increased in bilateral varicocele | [112] |
Prolactin-inducible protein (PIP) | Increased in oligoasthenozoospermia | [115] |
Increased in oligoasthenozoospermia | [123] | |
Decreased in NOA | [122] | |
Increased in azoospermia | [103] | |
Increased in patients with high levels of ROS | [111] | |
Absent in varicocele | [120] | |
Prostaglandin-H2-D-isomerase (PTGDS) | Decreased in oligoasthenozoospermia | [115] |
Highly decreased in OA | [108,127,128] | |
Prostate-specific antigen (KLK3) | Increased in oligoteratozoospermia | [117] |
Decreased in oligoasthenozoospermia | [115] | |
Decreased in varicocele | [120] | |
Prostate-specific antigen isoform 4 preprotein (KLK3 precursor) | Exclusively expressed in patients with high levels of ROS | [111] |
Prostatic-specific acid phosphatase (ACPP) | Increased in azoospermia | [103] |
Decreased in varicocele | [120] | |
Prostatic-specific acid phosphatase short isoform precursor (ACPP precursor) | Increased in patients with high levels of ROS | [111] |
Prostate-specific transglutaminase 4 (TGM4) | Increased in oligoasthenozoospermia | [115] |
Highly increased in asthenozoospermia | [23] | |
Protein/nucleic acid deglycase (DJ-1) | Absent in oligoteratozoospermia | [117] |
Highly decreased in asthenozoospermia | [129] | |
Semenogelin-1 (SEMG1) | Increased in oligoteratozoospermia | [117] |
Decreased in varicocele | [126] | |
Semenogelin-2 (SEMG2) | Decreased in varicocele | [126] |
Decreased in primary infertility | [114] | |
Semenogelin-2 precursor (SEMG2 precursor) | Increased in patients with high levels of ROS | [111] |
Serine/threonine protein kinase (SMG1) | Expressed exclusively in clinical varicocele | [120] |
Serum amyloid p-component (SAP) | Decreased in azoospermia, absent in patients with Sertoli cell-only syndrome | [116] |
Sorbitol dehydrogenase (SORD) | Expressed exclusively in NOA | [108] |
Decreased in asthenozoospermia | [89] | |
Extracellular Superoxide dismutase [Cu-Zn] (SOD3) | Decreased in oligoasthenozoospermia | [115] |
Superoxide-dismutase (SOD) | Decreased in azoospermia | [116] |
Tetraspanin-1 (TSPAN1), | Increased in oligoasthenozoospermia | [115] |
Transketolase-like protein 1 (TKTL1) | Expressed exclusively in fertile samples | [100] |
Tubulin-folding cofactor B (TBCB) | Increased in patients with oliagoasthenoteratozoospermia and high levels of ROS | [111] |
Zinc alpha-2 glycoprotein 1 (AZGP1) | Increased in oligozoospermia | [117] |
Decreased in oligoasthenozoospermia | [115] |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Candenas, L.; Chianese, R. Exosome Composition and Seminal Plasma Proteome: A Promising Source of Biomarkers of Male Infertility. Int. J. Mol. Sci. 2020, 21, 7022. https://doi.org/10.3390/ijms21197022
Candenas L, Chianese R. Exosome Composition and Seminal Plasma Proteome: A Promising Source of Biomarkers of Male Infertility. International Journal of Molecular Sciences. 2020; 21(19):7022. https://doi.org/10.3390/ijms21197022
Chicago/Turabian StyleCandenas, Luz, and Rosanna Chianese. 2020. "Exosome Composition and Seminal Plasma Proteome: A Promising Source of Biomarkers of Male Infertility" International Journal of Molecular Sciences 21, no. 19: 7022. https://doi.org/10.3390/ijms21197022