Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Metabolic Fingerprinting of Seminal Plasma from Non-obstructive Azoospermia Patients: Positive Versus Negative Sperm Retrieval

Authors
1 Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran; Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Med
2 Department of Medical Physics, Tarbiat Modares University, Tehran, Iran
3 Chemometrics and Chemoinformatics Laboratory, Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, Tehran, Iran
4 Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
5 Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
6 Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Metabolomics and Genomics Research Center, Endocrinol
Abstract
Background: Non-obstructive azoospermia (NOA) occurs in approximately 10% of infertile men. Retrieval of the spermatozoa from the testicle of NOA patients is an invasive approach. Seminal plasma is an excellent source for exploring to find the biomarkers for presence of spermatozoa in testicular tissue. The present discovery phase study aimed to use metabolic fingerprinting to detect spermatogenesis from seminal plasma in NOA patients as a non-invasive method. Methods: In this study, 20 men with NOA were identified based on histological analysis who had their first testicular biopsy in 2015 at Avicenna Fertility Center, Tehran, Iran. They were divided into two groups, a positive testicular sperm extraction (TESE(+)) and a negative testicular sperm extraction (TESE(-)). Seminal plasma of NOA patients was collected before they underwent testicular sperm extraction (TESE) operation. The metabolomic fingerprinting was evaluated by Raman spectrometer. Principal component analysis (PCA) and an unsupervised statistical method, was used to detect outliers and find the structure of the data. The PCA was analyzed by MATLAB software. Results: Metabolic fingerprinting of seminal plasma from NOA showed that TESE(+) versus TESE(-) patients were classified by PCA. Furthermore, a possible subdivision of TESE(-) group was observed. Additionally, TESE(-) patients were in extreme oxidative imbalance compared to TESE(+) patients. Conclusion: Metabolic fingerprinting of seminal plasma can be considered as a breakthrough, an easy and cheap method for prediction presence of spermatogenesis in NOA.
Keywords

  1. Thonneau P, Marchand S, Tallec A, Ferial M-L, Ducot B, Lansac J, et al. Incidence and main causes of infertility in a resident population (1 850 000) of three French regions (1988–1989). Hum Reprod. 1991;6(6):811-6.
  2. Costabile RA, Spevak M. Characterization of patients presenting with male factor infertility in an equal access, no cost medical system. Urology. 2001;58(6):1021-4.
  3. Donoso P, Tournaye H, Devroey P. Which is the best sperm retrieval technique for non-obstructive azoospermia? A systematic review. Hum Reprod Update. 2007;13(6):539-49.
  4. Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340(8810):17-8.
  5. Turek PJ, Johnson MH. A seminal molecular marker for sperm presence in non-obstructive azoospermia? Reprod Biomed Online. 2016;33(2):119-20.
  6. Raman JD, Schlegel PN. Testicular sperm extraction with intracytoplasmic sperm injection is successful for the treatment of nonobstructive azoospermia associated with cryptorchidism. J Urol. 2003;170(4):1287-90.
  7. Schlegel PN, Palermo GD, Goldstein M, Menendez S, Zaninovic N, Veeck LL, et al. Testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia. Urology. 1997;49(3):435-40.
  8. Seo JT, Ko WJ. Predictive factors of successful testicular sperm recovery in non‐obstructive azoospermia patients. Int J Androl. 2001;24(5):306-10.
  9. Kovac JR, Pastuszak AW, Lamb DJ. The use of genomics, proteomics, and metabolomics in identifying biomarkers of male infertility. Fertil Steril. 2013;99(4):998-1007.
  10. Minai‐Tehrani A, Jafarzadeh N, Gilany K. Metabolomics: a state‐of‐the‐art technology for better understanding of male infertility. Andrologia. 2016;48(6):609-16.
  11. Norvig P, Relman DA, Goldstein DB, Kammen DM, Weinberger DR, Aiello LC, et al. 2020 Visions. Nature. 2010;463(7):26-32.
  12. Villas-Boas SG, Nielsen J, Smedsgaard J, Hansen MA, Roessner-Tunali U. Metabolome analysis: an introduction. 1st ed. New Jesrsey: John Wiley & Sons; 2007. 289 p.
  13. Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, et al. HMDB 3.0--the human metabolome database in 2013. Nucleic Acids Res. 2013;(Database issue):D801-7.
  14. Jafarzadeh N, Mani-Varnosfaderani A, Minai-Tehrani A, Savadi-Shiraz E, Sadeghi MR, Gilany K. Metabolomics fingerprinting of seminal plasma from unexplained infertile men: a need for novel diagnostic biomarkers. Mol Reprod Dev. 2015;82(3):150.
  15. Gilany K, Moazeni‐Pourasil RS, Jafarzadeh N, Savadi‐Shiraz E. Metabolomics fingerprinting of the human seminal plasma of asthenozoospermic patients. Mol Reprod Dev. 2014;81(1):84-6.
  16. 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(2):61-71.
  17. Lynch MJ, Masters J, Pryor JP, Lindon JC, Spraul M, Foxall PJ, et al. Ultra high field NMR spectroscopic studies on human seminal fluid, seminal vesicle and prostatic secretions. J Pharm Biomed Anal. 1994;12(1):5-19.
  18. Hamamah S, Seguin F, Bujan L, Barthelemy C, Mieusset R, Lansac J. Quantification by magnetic resonance spectroscopy of metabolites in seminal plasma able to differentiate different forms of azoospermia. Hum Reprod. 1998;13(1):132-5.
  19. Aaronson DS, Iman R, Walsh TJ, Kurhanewicz J, Turek PJ. A novel application of 1H magnetic resonance spectroscopy: non-invasive identification of spermatogenesis in men with non-obstructive azoospermia. Hum Reprod. 2010;25(4):847-52.
  20. Gilany K, Mani‐Varnosfaderani A, Minai‐Tehrani A, Mirzajani F, Ghassempour A, Sadeghi MR, et al. Untargeted metabolomic profiling of seminal plasma in non‐obstructive azoospermia men: a non‐invasive detection of spermatogenesis. Biomed Chromatogr. 2017;31(8).
  21. Agarwal A, Gupta S, Sharma R. Andrological evaluation of male infertility. 1st ed. Switzerland: Springer; 2016. Reactive oxygen species (ROS) measurement; p. 155-63.
  22. Schill WB, Comhaire FH, Hargreave TB. Andrology for the Clinician.1st ed. New York: Springer Science+ Business Media; 2006. 632 p.
  23. Aitken RJ, Krausz C. Oxidative stress, DNA damage and the Y chromosome. Reproduction. 2001;122(4):497-506.
  24. Deepinder F, Chowdary HT, Agarwal A. Role of metabolomic analysis of biomarkers in the management of male infertility. Expert Rev Mol Diagn. 2007;7(4):351-8.
  25. Sakamoto Y, Ishikawa T, Kondo Y, Yamaguchi K, Fujisawa M. The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 2008;101(12):1547-52.
  26. Agarwal A, Sekhon LH. The role of antioxidant therapy in the treatment of male infertility. Hum Fertil (Camb). 2010;13(4):217-25.
  27. Lombardo F, Sansone A, Romanelli F, Paoli D, Gandini L, Lenzi A. The role of antioxidant therapy in the treatment of male infertility: an overview. Asian J Androl. 2011;13(5):690-7.