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Journals / Cumhuriyet Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi / 2024 / Volume: 9 Issue: 3

Potential Role of Exosomes in the Male Reproductive System

Erkek Üreme Sisteminde Eksozomların Potansiyel Rolü

Oya Korkmaz(MALATYA TURGUT ÖZAL ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0003-2923-5869
Mustafa Numan Bucak(SELÇUK ÜNİVERSİTESİ)0000-0002-2955-8599
Pages
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Publication Date
2024-12-31
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

By analysing current research findings on this topic, the knowledge on the contribution of exosomes to male reproductive health is highlighted.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Infertility is a reproductive disorder that can affect both men and women and has become a global health problem.
📊
Key Findings & Data:Approximately 50% of infertile cases are known to be caused by male reproductive disorders.
💡
Conclusion & Impact:By analysing current research findings on this topic, the knowledge on the contribution of exosomes to male reproductive health is highlighted.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:exosome · male infertility · spermatogenesis

Abstract

Infertility is a reproductive disorder that can affect both men and women and has become a global health problem. Approximately 50% of infertile cases are known to be caused by male reproductive disorders. Exosomes are nano-sized membrane vesicles secreted by a wide variety of cells and abundant in biological fluids, including semen. They contain lipids, proteins, microRNAs, and mRNAs and are known to play important roles in intracellular communication. Seminal exosomes mainly contain epididymosomes and prostasomes. Studies show that exosomes play a central role in regulating reproductive processes. The use of exosome therapy has significant potential in the treatment of infertility in patients. The amount of these membrane vesicles in biological fluids can be linked to physiological and pathological conditions. The molecular composition of seminal plasma and seminal exosomes, who regulates vesicle trafficking and fusion with spermatozoa, and what are the exosomal functions in sperm physiology remain unclear. This review focuses on discussing the effects of exosomes on the male reproductive system. By analysing current research findings on this topic, the knowledge on the contribution of exosomes to male reproductive health is highlighted.

Özet

İnfertilite hem erkekler de hem de kadınlarda görülebilen bir üreme sistemi bozukluğudur ve küresel bir sağlık sorunu haline gelmiştir. İnfertil vakaların yaklaşık %50'sinin erkek üreme bozukluklarından kaynaklandığı bilinmektedir. Eksozomlar, çok çeşitli hücreler tarafından salgılanan ve semen de dahil olmak üzere biyolojik sıvılarda bol miktarda bulunan nano boyutlu membran vezikülleridir. Lipidler, proteinler, mikroRNA'lar ve mRNA'lar içerirler ve hücre içi iletişimde önemli rol oynadıkları bilinmektedir. Seminal eksozomlar esas olarak epididimozomları ve prostasomları içerir. Yapılan çalışmalar, eksozomların üreme süreçlerini düzenlemede merkezi bir rol oynadığını göstermektedir. Eksozom tedavisinin kullanımı, hastalarda infertilite tedavisinde önemli bir potansiyele sahiptir. Bu membran veziküllerin biyolojik sıvılardaki miktarı, fizyolojik ve patolojik durumlarla bağlantılı olabilir. Seminal plazmanın ve seminal eksozomların moleküler bileşimi, vezikül trafiği ve spermatozoa ile füzyonunu kimin düzenlediği ve sperm fizyolojisindeki eksozomal işlevlerin neler olduğu hala belirsizliğini korumaya devam etmektedir. Bu derleme, eksozomların erkek üreme sistemi üzerindeki etkilerini tartışmaya odaklanmaktadır. Bu konudaki güncel araştırma bulguları analiz edilerek, erkek üreme sağlığı üzerindeki eksozomların katkısı hakkındaki bilgiler vurgulanmaktadır.

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Cite This Article

Korkmaz, O., Bucak, M. N. (2024). Potential Role of Exosomes in the Male Reproductive System. Cumhuriyet Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, Volume: 9 Issue: 3. https://doi.org/10.51754/cusbed.1572462

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References (125)

  1. Aalberts, M., Stout, T. A., & Stoorvogel, W. (2013). Prostasomes: extracellular vesicles from the prostate. Reproduction (Cambridge, England), 147(1), R1–R14. https://doi.org/10.1530/REP-13-0358
  2. Aalberts, M., Sostaric, E., Wubbolts, R., Wauben, M. W., Nolte-'t Hoen, E. N., Gadella, B. M., Stout, T. A., & Stoorvogel, W. (2013). Spermatozoa recruit prostasomes in response to capacitation induction. Biochimica et biophysica acta, 1834(11), 2326–2335. https://doi.org/10.1016/j.bbapap.2012.08.008
  3. Admyre, C., Johansson, S. M., Qazi, K. R., Filén, J. J., Lahesmaa, R., Norman, M., Neve, E. P., Scheynius, A., & Gabrielsson, S. (2007). Exosomes with immune modulatory features are present in human breast milk. Journal of immunology (Baltimore, Md.: 1950), 179(3), 1969–1978. https://doi.org/10.4049/jimmunol.179.3.1969
  4. Agarwal, A., Durairajanayagam, D., Halabi, J., Peng, J., & Vazquez-Levin, M. (2014). Proteomics, oxidative stress and male infertility. Reproductive biomedicine online, 29(1), 32–58. https://doi.org/10.1016/j.rbmo.2014.02.013
  5. Ahmed, N., Yufei, H., Yang, P., Muhammad Yasir, W., Zhang, Q., Liu, T., Hong, C., Lisi, H., Xiaoya, C., & Chen, Q. (2016). Cytological study on Sertoli cells and their interactions with germ cells during annual reproductive cycle in turtle. Ecology and evolution, 6(12), 4050–4064. https://doi.org/10.1002/ece3.2193
  6. Airola, M. V., & Hannun, Y. A. (2013). Sphingolipid metabolism and neutral sphingomyelinases. Handbook of experimental pharmacology, (215), 57–76. https://doi.org/10.1007/978-3-7091-1368-4_3
  7. Alasmari, W., Costello, S., Correia, J., Oxenham, S. K., Morris, J., Fernandes, L., Ramalho-Santos, J., Kirkman-Brown, J., Michelangeli, F., Publicover, S., & Barratt, C. L. (2013). Ca2+ signals generated by CatSper and Ca2+ stores regulate different behaviors in human sperm. The Journal of biological chemistry, 288(9), 6248–6258. https://doi.org/10.1074/jbc.M112.439356
  8. Amiri, N., Mohammadi, P., Allahgholi, A., Salek, F., & Amini, E. (2023). The potential of sertoli cells (SCs) derived exosomes and its therapeutic efficacy in male reproductive disorders. Life sciences, 312, 121251. https://doi.org/10.1016/j.lfs.2022.121251
  9. Arienti, G., Carlini, E., Nicolucci, A., Cosmi, E. V., Santi, F., & Palmerini, C. A. (1999a). The motility of human spermatozoa as influenced by prostasomes at various pH levels. Biology of the Cell, 91(1), 51-54.
  10. Aydos, O. S., Yukselten, Y., Ozkan, T., Ozkavukcu, S., Tuten Erdogan, M., Sunguroglu, A., & Aydos, K. (2023). Co-Culture of Cryopreserved Healthy Sertoli Cells with Testicular Tissue of Non-Obstructive Azoospermia (NOA) Patients in Culture Media Containing Follicle-Stimulating Hormone (FSH)/Testosterone Has No Advantage in Germ Cell Maturation. Journal of Clinical Medicine, 12(3), 1073. https://doi.org/10.3390/jcm12031073
  11. Baskaran, S., Selvam, M. K. P., & Agarwal, A. (2020). Exosomes of male reproduction. Advances in clinical chemistry, 95, 149-163. https://doi.org/10.1016/bs.acc.2019.08.004
  12. Bechoua, S., Rieu, I., Sion, B., & Grizard, G. (2011). Prostasomes as potential modulators of tyrosine phosphorylation in human spermatozoa. Systems Biology in Reproductive Medicine, 57(3), 139-148. https://doi.org/10.3109/19396368.2010.549538
  13. Belleannée, C., Calvo, É., Caballero, J., & Sullivan, R. (2013). Epididymosomes convey different repertoires of microRNAs throughout the bovine epididymis. Biology of reproduction, 89(2), 30. https://doi.org/10.1095/biolreprod.113.110486
  14. Breitbart, H., Cohen, G., & Rubinstein, S. (2005). Role of actin cytoskeleton in mammalian sperm capacitation and the acrosome reaction. Reproduction (Cambridge, England), 129(3), 263–268. https://doi.org/10.1530/rep.1.00269
  15. Brody, I., Ronquist, G., & Gottfries, A. (1983). Ultrastructural localization of the prostasome-an organelle in human seminal plasma. Upsala journal of medical sciences, 88(2), 63-80. https://doi.org/10.3109/03009738309178440
  16. Burden, H. P., Holmes, C. H., Persad, R., & Whittington, K. (2006). Prostasomes—their effects on human male reproduction and fertility. Human reproduction update, 12(3), 283-292. https://doi.org/10.1093/humupd/dmi052
  17. Caballero, J., Frenette, G., D'Amours, O., Belleannée, C., Lacroix‐Pepin, N., Robert, C., & Sullivan, R. (2012). Bovine sperm raft membrane associated glioma pathogenesis‐related 1‐like protein 1 (GliPr1L1) is modified during the epididymal transit and is potentially involved in sperm binding to the zona pellucida. Journal of cellular physiology, 227(12), 3876-3886. https://doi.org/10.1002/jcp.24099
  18. Castro, B. M., Prieto, M., & Silva, L. C. (2014). Ceramide: a simple sphingolipid with unique biophysical properties. Progress in lipid research, 54, 53-67. https://doi.org/10.1016/j.plipres.2014.01.004
  19. Chabory, E., Damon, C., Lenoir, A., Kauselmann, G., Kern, H., Zevnik, B., Garrel, C., Saez, F., Cadet, R., Henry-Berger, J., Schoor, M., Gottwald, U., Habenicht, U., Drevet, J. R., & Vernet, P. (2009). Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice. The Journal of clinical investigation, 119(7), 2074–2085. https://doi.org/10.1172/JCI38940
  20. Choy, K. H. K., Chan, S. Y., Lam, W., Jin, J., Zheng, T., Law, T. Y. S., Yu, S. S., Wang, W., Li, L., Xie, G., Yim, H. C. H., Chen, H., & Fok, E. K. L. (2022). The repertoire of testicular extracellular vesicle cargoes and their involvement in inter-compartmental communication associated with spermatogenesis. BMC biology, 20(1), 78. https://doi.org/10.1186/s12915-022-01268-5
  21. 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. (2019). Seminal plasma proteins and their relationship with sperm motility and morphology in boars. Andrologia, 51(4), e13222. https://doi.org/10.1111/and.13222
  22. Ding, Y., Ding, N., Zhang, Y., Xie, S., Huang, M., Ding, X., Dong, W., Zhang, Q., & Jiang, L. (2021). MicroRNA-222 Transferred From Semen Extracellular Vesicles Inhibits Sperm Apoptosis by Targeting BCL2L11. Frontiers in cell and developmental biology, 9, 736864. https://doi.org/10.3389/fcell.2021.736864
  23. Drabovich, A. P., Saraon, P., Jarvi, K., & Diamandis, E. P. (2014). Seminal plasma as a diagnostic fluid for male reproductive system disorders. Nature reviews. Urology, 11(5), 278–288. https://doi.org/10.1038/nrurol.2014.74
  24. Du, J., Shen, J., Wang, Y., Pan, C., Pang, W., Diao, H., & Dong, W. (2016). Boar seminal plasma exosomes maintain sperm function by infiltrating into the sperm membrane. Oncotarget, 7(37), 58832–58847. https://doi.org/10.18632/oncotarget.11315
  25. Duan, Y. G., Gong, J., Yeung, W. S. B., Haidl, G., & Allam, J. P. (2020). Natural killer and NKT cells in the male reproductive tract. Journal of reproductive immunology, 142, 103178. https://doi.org/10.1016/j.jri.2020.103178 Eickhoff, R., Baldauf, C., Koyro, H. W., Wennemuth, G., Suga, Y., Seitz, J., Henkel, R., & Meinhardt, A. (2004). 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. Molecular human reproduction, 10(8), 605–611. https://doi.org/10.1093/molehr/gah075
  26. Esfandyari, S., Elkafas, H., Chugh, R. M., Park, H. S., Navarro, A., & Al-Hendy, A. (2021). Exosomes as biomarkers for female reproductive diseases diagnosis and therapy. International journal of molecular sciences, 22(4), 2165. https://doi.org/10.3390/ijms22042165
  27. Fraser L. R. (2010). The "switching on" of mammalian spermatozoa: molecular events involved in promotion and regulation of capacitation. Molecular reproduction and development, 77(3), 197–208. https://doi.org/10.1002/mrd.21124
  28. Frenette, G., Lessard, C., & Sullivan, R. (2002). Selected proteins of “prostasome-like particles” from epididymal cauda fluid are transferred to epididymal caput spermatozoa in bull. Biology of reproduction, 67(1), 308-313. https://doi.org/10.1095/biolreprod67.1.308
  29. Frenette, G., Légaré, C., Saez, F., & Sullivan, R. (2005). Macrophage migration inhibitory factor in the human epididymis and semen. Molecular human reproduction, 11(8), 575-582. https://doi.org/10.1093/molehr/gah197
  30. Frenette, G., Thabet, M., & Sullivan, R. (2006). Polyol pathway in human epididymis and semen. Journal of andrology, 27(2), 233–239. https://doi.org/10.2164/jandrol.05108
  31. Fornés, M. W., Barbieri, A., & Cavicchia, J. C. (1995). Morphological and enzymatic study of membrane-bound vesicles from the lumen of the rat epididymis. Andrologia, 27(1), 1–5. https://doi.org/10.1111/j.1439-0272.1995.tb02087.x
  32. Gao, H., Cao, H., Li, Z., Li, L., Guo, Y., Chen, Y., Peng, G., Zeng, W., Du, J., Dong, W., & Yang, F. (2023). Exosome-derived Small RNAs in mouse Sertoli cells inhibit spermatogonial apoptosis. Theriogenology, 200, 155–167. https://doi.org/10.1016/j.theriogenology.2023.02.011
  33. 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 Apr-Jun;16(2):61-71.
  34. Griffiths, G. S., Miller, K. A., Galileo, D. S., & Martin-DeLeon, P. A. (2008). Murine SPAM1 is secreted by the estrous uterus and oviduct in a form that can bind to sperm during capacitation: acquisition enhances hyaluronic acid-binding ability and cumulus dispersal efficiency. Reproduction (Cambridge, England), 135(3), 293–301. https://doi.org/10.1530/REP-07-0340
  35. Girouard, J., Frenette, G., & Sullivan, R. (2011). Comparative proteome and lipid profiles of bovine epididymosomes collected in the intraluminal compartment of the caput and cauda epididymidis. International journal of andrology, 34(5 Pt 2), e475–e486. https://doi.org/10.1111/j.1365-2605.2011.01203.x
  36. Goossens, E., Jahnukainen, K., Mitchell, R. T., van Pelt, A., Pennings, G., Rives, N., Poels, J., Wyns, C., Lane, S., Rodriguez-Wallberg, K. A., Rives, A., Valli-Pulaski, H., Steimer, S., Kliesch, S., Braye, A., Andres, M. M., Medrano, J., Ramos, L., Kristensen, S. G., Andersen, C. Y., … Stukenborg, J. B. (2020). Fertility preservation in boys: recent developments and new insights. Human reproduction open, 2020(3), hoaa016. https://doi.org/10.1093/hropen/hoaa016
  37. Gurunathan, S., Kang, M. H., & Kim, J. H. (2021). A Comprehensive Review on Factors Influences Biogenesis, Functions, Therapeutic and Clinical Implications of Exosomes. International journal of nanomedicine, 16, 1281–1312. https://doi.org/10.2147/IJN.S291956
  38. Haigler, H. T., & Christmas, P. (1990). Annexin 1 is secreted by the human prostate. Biochemical Society transactions, 18(6), 1104–1106. https://doi.org/10.1042/bst0181104
  39. Houali, K., Wang, X., Shimizu, Y., Djennaoui, D., Nicholls, J., Fiorini, S., Bouguermouh, A., & Ooka, T. (2007). A new diagnostic marker for secreted Epstein-Barr virus encoded LMP1 and BARF1 oncoproteins in the serum and saliva of patients with nasopharyngeal carcinoma. Clinical cancer research: an official journal of the American Association for Cancer Research, 13(17), 4993–5000. https://doi.org/10.1158/1078-0432.CCR-06-2945
  40. Ibtisham, F., Wu, J., Xiao, M., An, L., Banker, Z., Nawab, A., Zhao, Y., & Li, G. (2017). Progress and future prospect of in vitro spermatogenesis. Oncotarget, 8(39):66709-66727. https://doi.org/10.18632/oncotarget.19640 James, E. R., Carrell, D. T., Aston, K. I., Jenkins, T. G., Yeste, M., & Salas-Huetos, A. (2020). The Role of the Epididymis and the Contribution of Epididymosomes to Mammalian Reproduction. International journal of molecular sciences, 21(15), 5377. https://doi.org/10.3390/ijms21155377
  41. Jodar, M., Soler-Ventura, A., Oliva, R., & Molecular Biology of Reproduction and Development Research Group (2017). Semen proteomics and male infertility. Journal of proteomics, 162, 125–134. https://doi.org/10.1016/j.jprot.2016.08.018
  42. Johnson, M.H. (2018). Sperm and eggs. In Essential Reproduction, 8th ed.; Wiley Blackwell: Hoboken, NJ, USA, 183, 196.
  43. Joshi, C. S., Khan, S. A., & Khole, V. V. (2014). Regulation of acrosome reaction by Liprin α3, LAR and its ligands in mouse spermatozoa. Andrology, 2(2), 165–174. https://doi.org/10.1111/j.2047-2927.2013.00167
  44. Keller, S., Rupp, C., Stoeck, A., Runz, S., Fogel, M., Lugert, S., Hager, H. D., Abdel-Bakky, M. S., Gutwein, P., & Altevogt, P. (2007). CD24 is a marker of exosomes secreted into urine and amniotic fluid. Kidney international, 72(9), 1095–1102. https://doi.org/10.1038/sj.ki.5002486
  45. Kelly R. W. (1995). Immunosuppressive mechanisms in semen: implications for contraception. Human reproduction (Oxford, England), 10(7), 1686–1693. https://doi.org/10.1093/oxfordjournals.humrep.a136156 Kharazi, U., & Badalzadeh, R. (2020). A review on the stem cell therapy and an introduction to exosomes as a new tool in reproductive medicine. Reproductive biology, 20(4), 447–459. https://doi.org/10.1016/j.repbio.2020.07.002
  46. Kirchhoff, C., & Hale, G. (1996). Cell-to-cell transfer of glycosylphosphatidylinositol-anchored membrane proteins during sperm maturation. Molecular human reproduction, 2(3), 177–184. https://doi.org/10.1093/molehr/2.3.177
  47. Kitamura, M., Namiki, M., Matsumiya, K., Tanaka, K., Matsumoto, M., Hara, T., Kiyohara, H., Okabe, M., Okuyama, A., & Seya, T. (1995). Membrane cofactor protein (CD46) in seminal plasma is a prostasome-bound form with complement regulatory activity and measles virus neutralizing activity. Immunology, 84(4), 626–632. Kotaja N. (2014). MicroRNAs and spermatogenesis. Fertility and sterility, 101(6), 1552–1562. https://doi.org/10.1016/j.fertnstert.2014.04.025
  48. Kowalczyk, A., Wrzecińska, M., Czerniawska-Piątkowska, E., & Kupczyński, R. (2022). Exosomes - Spectacular role in reproduction. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 148, 112752. https://doi.org/10.1016/j.biopha.2022.112752
  49. Krapf, D., Ruan, Y.C., Wertheimer, E.V., Battistone, M.A., Pawlak, J.B., Sanjay, A., Pilder, S.H., Cuasnicu, P., Breton, S., & Visconti, P.E. (2012). cSrc is necessary for epididymal development and is incorporated into sperm during epididymal transit. Dev Biol. 369(1):43-53. https://doi.org/10.1016/j.ydbio.2012.06.017
  50. Kravets, F. G., Lee, J., Singh, B., Trocchia, A., Pentyala, S. N., & Khan, S. A. (2000). Prostasomes: current concepts. The Prostate, 43(3), 169–174. https://doi.org/10.1002/(sici)1097-0045(20000515)43:3 3.0.co;2-d
  51. Kumar, A., Pandita, S., Laxmi, N. A., Bhakat, M., & Mohanty, T. K. (2019). Effects of prostasomes on functional parameters of fresh and cryopreservedthawed spermatozoa of crossbred Karan Fries (KF) bulls. Indian Journal of Animal Research, 53(9), 1167-1171. https://doi.org/10.18805/ijar.B-3665.
  52. Lange-Consiglio, A., Capra, E., Monferrini, N., Canesi, S., Bosi, G., Cretich, M., Frigerio, R., Galbiati, V., Bertuzzo, F., Cobalchini, F., Cremonesi, F., & Gasparrini, B. (2022). Extracellular vesicles from seminal plasma to improve fertilizing capacity of bulls. Reproduction & fertility, 3(4), 313–327. Advance online publication. https://doi.org/10.1530/RAF-22-0037
  53. Li, Q., Li, H., Liang, J., Mei, J., Cao, Z., Zhang, L., Luo, J., Tang, Y., Huang, R., Xia, H., Zhang, Q., Xiang, Q., Yang, Y., & Huang, Y. (2021). Sertoli cell-derived exosomal MicroRNA-486-5p regulates differentiation of spermatogonial stem cell through PTEN in mice. Journal of cellular and molecular medicine, 25(8), 3950–3962. https://doi.org/10.1111/jcmm.16347
  54. Liang, J., Li, H., Mei, J., Cao, Z., Tang, Y., Huang, R., Xia, H., Zhang, Q., Xiang, Q., Yang, Y., & Huang, Y. (2021). Sertoli cell-derived exosome-mediated transfer of miR-145-5p inhibits Leydig cell steroidogenesis by targeting steroidogenic factor 1. Federation of american societies for experimental biology journal, 35(6):e21660. https://doi.org/10.1096/fj.202002589RRRR
  55. Lin, Y., Liang, A., He, Y., Li, Z., Li, Z., Wang, G., & Sun, F. (2019). Proteomic analysis of seminal extracellular vesicle proteins involved in asthenozoospermia by iTRAQ. Molecular reproduction and development, 86(9), 1094–1105. https://doi.org/10.1002/mrd.23224
  56. Ma, Y., Zhou, Y., Xiao, Q., Zou, S. S., Zhu, Y. C., Ping, P., & Chen, X. F. (2021). Seminal exosomal miR-210-3p as a potential marker of Sertoli cell damage in Varicocele. Andrology, 9(1), 451–459. https://doi.org/10.1111/andr.12913
  57. Ma, Y., Zhou, Y., Zou, S. S., Sun, Y., & Chen, X. F. (2022). Exosomes released from Sertoli cells contribute to the survival of Leydig cells through CCL20 in rats Molecular human reproduction, 28(2), gaac002. https://doi.org/10.1093/molehr/gaac002
  58. Machtinger, R., Laurent, L. C., & Baccarelli, A. A. (2016). Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Human reproduction update, 22(2), 182–193. https://doi.org/10.1093/humupd/dmv055
  59. Martin-DeLeon P. A. (2006). Epididymal SPAM1 and its impact on sperm function. Molecular and cellular endocrinology, 250(1-2), 114–121. https://doi.org/10.1016/j.mce.2005.12.033
  60. Mathivanan, S., Fahner, C. J., Reid, G. E., & Simpson, R. J. (2012). ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic acids research, 40(Database issue), D1241–D1244. https://doi.org/10.1093/nar/gkr828
  61. Miksa, M., Wu, R., Dong, W., Komura, H., Amin, D., Ji, Y., Wang, Z., Wang, H., Ravikumar, T. S., Tracey, K. J., & Wang, P. (2009). Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor-factor VIII [corrected]. Journal of immunology (Baltimore, Md.: 1950), 183(9), 5983–5990. https://doi.org/10.4049/jimmunol.0802994
  62. Milardi, D., Grande, G., Vincenzoni, F., Messana, I., Pontecorvi, A., De Marinis, L., Castagnola, M., & Marana, R. (2012). Proteomic approach in the identification of fertility pattern in seminal plasma of fertile men. Fertility and sterility, 97(1), 67–73.e1. https://doi.org/10.1016/j.fertnstert.2011.10.013
  63. Minelli, A., Allegrucci, C., Liguori, L., & Ronquist, G. (2002). Ecto-diadenosine polyphosphates hydrolase activity on human prostasomes. The Prostate, 51(1), 1–9. https://doi.org/10.1002/pros.10062
  64. Murdica, V., Giacomini, E., Alteri, A., Bartolacci, A., Cermisoni, G. C., Zarovni, N., Papaleo, E., Montorsi, F., Salonia, A., Viganò, P., & Vago, R. (2019). Seminal plasma of men with severe asthenozoospermia contain exosomes that affect spermatozoa motility and capacitation. Fertility and sterility, 111(5), 897–908.e2. https://doi.org/10.1016/j.fertnstert.2019.01.030
  65. Mobarak, H., Heidarpour, M., Lolicato, F., Nouri, M., Rahbarghazi, R., & Mahdipour, M. (2019). Physiological impact of extracellular vesicles on female reproductive system; highlights to possible restorative effects on female age-related fertility. BioFactors (Oxford, England), 45(3), 293–303. https://doi.org/10.1002/biof.1497
  66. Mobarak, H., Heidarpour, M., Rahbarghazi, R., Nouri, M., & Mahdipour, M. (2021). Amniotic fluid-derived exosomes improved spermatogenesis in a rat model of azoospermia. Life sciences, 274, 119336. https://doi.org/10.1016/j.lfs.2021.119336
  67. Neto, F. T., Bach, P. V., Najari, B. B., Li, P. S., & Goldstein, M. (2016). Spermatogenesis in humans and its affecting factors. Seminars in cell & developmental biology, 59, 10–26. https://doi.org/10.1016/j.semcdb.2016.04.009
  68. Ni, F. D., Hao, S. L., & Yang, W. X. (2019). Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis. Cell death & disease, 10(8), 541. https://doi.org/10.1038/s41419-019-1782-z
  69. Nilsson, J., Skog, J., Nordstrand, A., Baranov, V., Mincheva-Nilsson, L., Breakefield, X. O., & Widmark, A. (2009). Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. British journal of cancer, 100(10), 1603–1607. https://doi.org/10.1038/sj.bjc.6605058
  70. Oh, J. S., Han, C., & Cho, C. (2009). ADAM7 is associated with epididymosomes and integrated into sperm plasma membrane. Molecules and cells, 28(5), 441–446. https://doi.org/10.1007/s10059-009-0140-x
  71. Oliver, E., & Stukenborg, J. B. (2020). Rebuilding the human testis in vitro. Andrology, 8(4), 825–834. https://doi.org/10.1111/andr.12710
  72. Park KH, Kim BJ, Kang J, Nam TS, Lim JM, Kim HT, Park JK, Kim YG, Chae SW, Kim UH. Ca2+ signaling tools acquired from prostasomes are required for progesterone-induced sperm motility. Sci Signal. 2011 May 17;4(173):ra31.
  73. Patil, S. M., Sawant, S. S., & Kunda, N. K. (2020). Exosomes as drug delivery systems: A brief overview and progress update. European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 154, 259–269. https://doi.org/10.1016/j.ejpb.2020.07.026
  74. Paul, N., Talluri, T. R., Nag, P., & Kumaresan, A. (2021). Epididymosomes: A potential male fertility influencer. Andrologia, 53(9), e14155. https://doi.org/10.1111/and.14155
  75. Pelzman, D. L., Orwig, K. E., & Hwang, K. (2020). Progress in translational reproductive science: testicular tissue transplantation and in vitro spermatogenesis. Fertility and sterility, 113(3), 500–509. https://doi.org/10.1016/j.fertnstert.2020.01.038
  76. Perez-Hernandez, D., Gutiérrez-Vázquez, C., Jorge, I., López-Martín, S., Ursa, A., Sánchez-Madrid, F., Vázquez, J., & Yáñez-Mó, M. (2013). The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. The Journal of biological chemistry, 288(17), 11649–11661. https://doi.org/10.1074/jbc.M112.445304
  77. Raposo, G., Nijman, H. W., Stoorvogel, W., Liejendekker, R., Harding, C. V., Melief, C. J., & Geuze, H. J. (1996). B lymphocytes secrete antigen-presenting vesicles. The Journal of experimental medicine, 183(3), 1161–1172. https://doi.org/10.1084/jem.183.3.1161
  78. Rejraji, H., Vernet, P., & Drevet, J. R. (2002). GPX5 is present in the mouse caput and cauda epididymidis lumen at three different locations. Molecular reproduction and development, 63(1), 96–103. https://doi.org/10.1002/mrd.10136
  79. Richer, G., Baert, Y., & Goossens, E. (2020). In-vitro spermatogenesis through testis modelling: Toward the generation of testicular organoids. Andrology, 8(4), 879–891. https://doi.org/10.1111/andr.12741
  80. Ronquist G. (2012). Prostasomes are mediators of intercellular communication: from basic research to clinical implications. Journal of internal medicine, 271(4), 400–413. https://doi.org/10.1111/j.1365-2796.2011.02487.x
  81. Ronquist, K. G., Ek, B., Morrell, J., Stavreus-Evers, A., Ström Holst, B., Humblot, P., Ronquist, G., & Larsson, A. (2013). Prostasomes from four different species are able to produce extracellular adenosine triphosphate (ATP). Biochimica et biophysica acta, 1830(10), 4604–4610. https://doi.org/10.1016/j.bbagen.2013.05.019
  82. Ronquist, K. G., Sanchez, C., Dubois, L., Chioureas, D., Fonseca, P., Larsson, A., Ullén, A., Yachnin, J., Ronquist, G., & Panaretakis, T. (2016). Energy-requiring uptake of prostasomes and PC3 cell-derived exosomes into non-malignant and malignant cells. Journal of extracellular vesicles, 5, 29877. https://doi.org/10.3402/jev.v5.29877
  83. Rowlison, T., Cleland, T. P., Ottinger, M. A., & Comizzoli, P. (2020). Novel Proteomic Profiling of Epididymal Extracellular Vesicles in the Domestic Cat Reveals Proteins Related to Sequential Sperm Maturation with Differences Observed between Normospermic and Teratospermic Individuals. Molecular & cellular proteomics: MCP, 19(12), 2090–2104. https://doi.org/10.1074/mcp.RA120.002251
  84. Salek, F., Baharara, J., Shahrokhabadi, K. N., & Amini, E. (2021). The guardians of germ cells; Sertoli-derived exosomes against electromagnetic field-induced oxidative stress in mouse spermatogonial stem cells. Theriogenology, 173, 112–122. https://doi.org/10.1016/j.theriogenology.2021.08.001
  85. Samanta, L., Parida, R., Dias, T. R., & Agarwal, A. (2018). The enigmatic seminal plasma: a proteomics insight from ejaculation to fertilization. Reproductive biology and endocrinology: RB&E, 16(1), 41. https://doi.org/10.1186/s12958-018-0358-6
  86. Schlatt, S., & Ehmcke, J. (2014). Regulation of spermatogenesis: an evolutionary biologist's perspective. Seminars in cell & developmental biology, 29, 2–16. https://doi.org/10.1016/j.semcdb.2014.03.007 Sherif, I. O., Sabry, D., Abdel-Aziz, A., & Sarhan, O. M. (2018). The role of mesenchymal stem cells in chemotherapy-induced gonadotoxicity. Stem cell research & therapy, 9(1), 196. https://doi.org/10.1186/s13287-018-0946-6
  87. Sinha, D., Roy, S., Saha, P., Chatterjee, N., & Bishayee, A. (2021). Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy. Cancers, 13(2), 326. https://doi.org/10.3390/cancers13020326
  88. Skibinski, G., Kelly, R. W., Harkiss, D., & James, K. (1992). Immunosuppression by human seminal plasma--extracellular organelles (prostasomes) modulate activity of phagocytic cells. American journal of reproductive immunology (New York, N.Y.: 1989), 28(2), 97–103. https://doi.org/10.1111/j.1600-0897.1992.tb00767.x
  89. Skryabin, G. O., Komelkov, A. V., Savelyeva, E. E., & Tchevkina, E. M. (2020). Lipid Rafts in Exosome Biogenesis. Biochemistry. Biokhimiia, 85(2), 177–191. https://doi.org/10.1134/S0006297920020054
  90. Sousa, C., Pereira, I., Santos, A. C., Carbone, C., Kovačević, A. B., Silva, A. M., & Souto, E. B. (2017). Targeting dendritic cells for the treatment of autoimmune disorders. Colloids and surfaces. B, Biointerfaces, 158, 237–248. https://doi.org/10.1016/j.colsurfb.2017.06.050
  91. Sullivan R. (2016). Epididymosomes: Role of extracellular microvesicles in sperm maturation. Frontiers in bioscience (Scholar edition), 8(1), 106–114. https://doi.org/10.2741/s450
  92. Sullivan, R., & Saez, F. (2013). Epididymosomes, prostasomes, and liposomes: their roles in mammalian male reproductive physiology. Reproduction (Cambridge, England), 146(1), R21–R35. https://doi.org/10.1530/REP-13-0058
  93. Sullivan, R., Saez, F., Girouard, J., & Frenette, G. (2005). Role of exosomes in sperm maturation during the transit along the male reproductive tract. Blood cells, molecules & diseases, 35(1), 1–10. https://doi.org/10.1016/j.bcmd.2005.03.005
  94. Tamessar, C. T., Trigg, N. A., Nixon, B., Skerrett-Byrne, D. A., Sharkey, D. J., Robertson, S. A., Bromfield, E. G., & Schjenken, J. E. (2021). Roles of male reproductive tract extracellular vesicles in reproduction. American journal of reproductive immunology (New York, N.Y.: 1989), 85(2), e13338. https://doi.org/10.1111/aji.13338
  95. Tannetta, D., Dragovic, R., Alyahyaei, Z., & Southcombe, J. (2014). Extracellular vesicles and reproduction-promotion of successful pregnancy. Cellular & molecular immunology, 11(6), 548–563. https://doi.org/10.1038/cmi.2014.42
  96. Tarazona, R., Delgado, E., Guarnizo, M. C., Roncero, R. G., Morgado, S., Sánchez-Correa, B., Gordillo, J. J., Dejulián, J., & Casado, J. G. (2011). Human prostasomes express CD48 and interfere with NK cell function. Immunobiology, 216(1-2), 41–46. https://doi.org/10.1016/j.imbio.2010.03.002
  97. Thiageswaran, S., Steele, H., Voigt, A. L., & Dobrinski, I. (2022). A Role for Exchange of Extracellular Vesicles in Porcine Spermatogonial Co-Culture. International journal of molecular sciences, 23(9), 4535. https://doi.org/10.3390/ijms23094535
  98. Thimon, V., Frenette, G., Saez, F., Thabet, M., & Sullivan, R. (2008). Protein composition of human epididymosomes collected during surgical vasectomy reversal: a proteomic and genomic approach. Human reproduction (Oxford, England), 23(8), 1698–1707. https://doi.org/10.1093/humrep/den181
  99. Tran, K. T. D., Valli-Pulaski, H., Colvin, A., & Orwig, K. E. (2022). Male fertility preservation and restoration strategies for patients undergoing gonadotoxic therapies†. Biology of reproduction, 107(2), 382–405. https://doi.org/10.1093/biolre/ioac072
  100. Utleg, A. G., Yi, E. C., Xie, T., Shannon, P., White, J. T., Goodlett, D. R., Hood, L., & Lin, B. (2003). Proteomic analysis of human prostasomes. The Prostate, 56(2), 150–161. https://doi.org/10.1002/pros.10255
  101. Van den Boorn, J. G., Dassler, J., Coch, C., Schlee, M., & Hartmann, G. (2013). Exosomes as nucleic acid nanocarriers. Advanced drug delivery reviews, 65(3), 331–335. https://doi.org/10.1016/j.addr.2012.06.011
  102. Vasan S. S. (2011). Semen analysis and sperm function tests: How much to test?. Indian journal of urology: IJU: journal of the Urological Society of India, 27(1), 41–48. https://doi.org/10.4103/0970-1591.78424
  103. Vernet, P., Aitken, R. J., & Drevet, J. R. (2004). Antioxidant strategies in the epididymis. Molecular and cellular endocrinology, 216(1-2), 31–39. https://doi.org/10.1016/j.mce.2003.10.069
  104. Vickram, A. S., Srikumar, P. S., Srinivasan, S., Jeyanthi, P., Anbarasu, K., Thanigaivel, S., Nibedita, D., Jenila Rani, D., & Rohini, K. (2021). Seminal exosomes - An important biological marker for various disorders and syndrome in human reproduction. Saudi journal of biological sciences, 28(6), 3607–3615. https://doi.org/10.1016/j.sjbs.2021.03.038
  105. Vickram, A. S., Anbarasu, K., Gulothungan, G., Thanigaivel, S., Nanmaran, R., & Palanivelu, J. (2022). Characterization of human prostasomes protein Clusterin (macromolecule) - a novel biomarker for male infertility diagnosis and prognosis. Journal of biomolecular structure & dynamics, 40(9), 3979–3988. https://doi.org/10.1080/07391102.2020.1852960
  106. Vivacqua, A., Siciliano, L., Sabato, M., Palma, A., & Carpino, A. (2004). Prostasomes as zinc ligands in human seminal plasma. International journal of andrology, 27(1), 27–31. https://doi.org/10.1111/j.1365-2605.2004.00441.x
  107. Wang, G. J., Liu, Y., Qin, A., Shah, S. V., Deng, Z. B., Xiang, X., Cheng, Z., Liu, C., Wang, J., Zhang, L., Grizzle, W. E., & Zhang, H. G. (2008). Thymus exosomes-like particles induce regulatory T cells. Journal of immunology (Baltimore, Md.: 1950), 181(8), 5242–5248. https://doi.org/10.4049/jimmunol.181.8.5242
  108. Wang, B., Zhai, C., Li, Y., Ma, B., Li, Z., & Wang, J. (2023). Sertoli cells-derived exosomal miR-30a-5p regulates ubiquitin E3 ligase Zeb2 to affect the spermatogonial stem cells proliferation and differentiation. Reproductive toxicology (Elmsford, N.Y.), 117, 108340. https://doi.org/10.1016/j.reprotox.2023.108340
  109. 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. Yellon, D. M., & Davidson, S. M. (2014). Exosomes: nanoparticles involved in cardioprotection?. Circulation research, 114(2), 325–332. https://doi.org/10.1161/CIRCRESAHA.113.300636
  110. Zakharova, L., Svetlova, M., & Fomina, A. F. (2007). T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. Journal of cellular physiology, 212(1), 174–181. https://doi.org/10.1002/jcp.21013
  111. Quadri, Z., Elsherbini, A., & Bieberich, E. (2022). Extracellular vesicles in pharmacology: Novel approaches in diagnostics and therapy. Pharmacological research, 175, 105980. https://doi.org/10.1016/j.phrs.2021.105980
  112. 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., & Liu, C. D. (2017). Comprehensive proteomics analysis of exosomes derived from human seminal plasma. Andrology, 5(5), 1007–1015. https://doi.org/10.1111/andr.12412
  113. Yeung, C. H., Cooper, T. G., Schröter, S., Kirchhoff, C., & Nieschlag, E. (1998). Epididymal secretion of CD52 as measured in human seminal plasma by a fluorescence immunoassay. Molecular human reproduction, 4(5), 447–451. https://doi.org/10.1093/molehr/4.5.447
  114. Yu, K., Xiao, K., Sun, Q. Q., Liu, R. F., Huang, L. F., Zhang, P. F., Xu, H. Y., Lu, Y. Q., & Fu, Q. (2023). Comparative proteomic analysis of seminal plasma exosomes in buffalo with high and low sperm motility. BMC genomics, 24(1), 8. https://doi.org/10.1186/s12864-022-09106-2
  115. Yue, D., Yang, R., Xiong, C., & Yang, R. (2022). Functional prediction and profiling of exosomal circRNAs derived from seminal plasma for the diagnosis and treatment of oligoasthenospermia. Experimental and therapeutic medicine, 24(5), 649. https://doi.org/10.3892/etm.2022.11586
  116. Admyre, C., Johansson, S. M., Qazi, K. R., Filén, J. J., Lahesmaa, R., Norman, M., Neve, E. P., Scheynius, A., & Gabrielsson, S. (2007). Exosomes with immune modulatory features are present in human breast milk. Journal of immunology (Baltimore, Md.: 1950), 179(3), 1969–1978. https://doi.org/10.4049/jimmunol.179.3.1969
  117. Houali, K., Wang, X., Shimizu, Y., Djennaoui, D., Nicholls, J., Fiorini, S., Bouguermouh, A., & Ooka, T. (2007). A new diagnostic marker for secreted Epstein-Barr virus encoded LMP1 and BARF1 oncoproteins in the serum and saliva of patients with nasopharyngeal carcinoma. Clinical cancer research: an official journal of the American Association for Cancer Research, 13(17), 4993–5000. https://doi.org/10.1158/1078-0432.CCR-06-2945
  118. Miksa, M., Wu, R., Dong, W., Komura, H., Amin, D., Ji, Y., Wang, Z., Wang, H., Ravikumar, T. S., Tracey, K. J., & Wang, P. (2009). Immature dendritic cell-derived exosomes rescue septic animals via milk fat globule epidermal growth factor-factor VIII [corrected]. Journal of immunology (Baltimore, Md.: 1950), 183(9), 5983–5990. https://doi.org/10.4049/jimmunol.0802994
  119. Patil, S. M., Sawant, S. S., & Kunda, N. K. (2020). Exosomes as drug delivery systems: A brief overview and progress update. European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 154, 259–269. https://doi.org/10.1016/j.ejpb.2020.07.026
  120. Rowlison, T., Cleland, T. P., Ottinger, M. A., & Comizzoli, P. (2020). Novel Proteomic Profiling of Epididymal Extracellular Vesicles in the Domestic Cat Reveals Proteins Related to Sequential Sperm Maturation with Differences Observed between Normospermic and Teratospermic Individuals. Molecular & cellular proteomics: MCP, 19(12), 2090–2104. https://doi.org/10.1074/mcp.RA120.002251
  121. Samanta, L., Parida, R., Dias, T. R., & Agarwal, A. (2018). The enigmatic seminal plasma: a proteomics insight from ejaculation to fertilization. Reproductive biology and endocrinology: RB&E, 16(1), 41. https://doi.org/10.1186/s12958-018-0358-6
  122. Skibinski, G., Kelly, R. W., Harkiss, D., & James, K. (1992). Immunosuppression by human seminal plasma--extracellular organelles (prostasomes) modulate activity of phagocytic cells. American journal of reproductive immunology (New York, N.Y.: 1989), 28(2), 97–103. https://doi.org/10.1111/j.1600-0897.1992.tb00767.x
  123. Tamessar, C. T., Trigg, N. A., Nixon, B., Skerrett-Byrne, D. A., Sharkey, D. J., Robertson, S. A., Bromfield, E. G., & Schjenken, J. E. (2021). Roles of male reproductive tract extracellular vesicles in reproduction. American journal of reproductive immunology (New York, N.Y.: 1989), 85(2), e13338. https://doi.org/10.1111/aji.13338
  124. Vasan S. S. (2011). Semen analysis and sperm function tests: How much to test?. Indian journal of urology: IJU: journal of the Urological Society of India, 27(1), 41–48. https://doi.org/10.4103/0970-1591.78424
  125. Wang, G. J., Liu, Y., Qin, A., Shah, S. V., Deng, Z. B., Xiang, X., Cheng, Z., Liu, C., Wang, J., Zhang, L., Grizzle, W. E., & Zhang, H. G. (2008). Thymus exosomes-like particles induce regulatory T cells. Journal of immunology (Baltimore, Md.: 1950), 181(8), 5242–5248. https://doi.org/10.4049/jimmunol.181.8.5242