Year 2019 Vol. 27 No 6

UROLOGY

Y.A. NAKONECHNYI 1, A.M. HAVRYLYUK 1, A.Y. NAKONECHNYI 1, V.V. CHOPYAK 1, M.Ì. KURPISZ 2

IMMUNOPATHOGENETIC PROGNOSTIC MARKERS OF THE FERTILE POTENTIAL IN MEN WITH LEFT-SIDED VARICOCELE

Danylo Halytsky Lviv National Medical University 1, Lviv,
Ukraine,
Institute of Human Genetics Polish Academy of Sciences 2, Poznan,
Poland

Objective. To determine immunopathogenetic prognostic markers of the fertile potential in men with varicocele by the nature of changes in the induces of congenital and acquired immunity, to assess their trends after varicocelectomy in the context of maintaining the risk of infertility development.
Methods. 36 patients with the left-sided varicocele grade II-III and 25 patients after laparoscopic varicocelectomy underwent an immunological study. The control group consisted of 23 healthy men. The participants’ age was 19-33 years. The cytokines concentration in the blood and seminal fluid were determined by ELISA. Flow cytometry was used for immunophenotyping of peripheral blood lymphocytes (absolute and relative numbers).
Results. In patients with the left-sided varicocele grade II-III concentration of cytokines in the peripheral blood and seminal fluid significantly differed from the subjects of the control group. Statistically significant differences were found in the concentration of various cytokines and quantitative indicators of the cellular level of acquired immunity in comparison to practically healthy men. Levels of the most cytokines in the serum of the peripheral blood and seminal fluid, quantitative indicators of lymphocyte populations, subpopulations of T-lymphocytes and their activation markers in the peripheral blood normalized three months after laparoscopic varicocelectomy.
ROC analysis of cytokine levels in the peripheral blood serum and seminal fluid in patients with varicocele grade II-III revealed a number of patterns. Significant immunopathogenetic prognostic markers of the fertile potential could be an increase of IFN-γ levels more than 12.4 pg/ml in the peripheral blood serum, as well as levels of interleukins in the seminal fluid: for spIL-1β 50.4 pg/ml and less, for spIL-6 more than 49.5 pg/ml.
Conclusions. Cytokine regulation changes in the reproductive and immune systems, determined by the imbalance in concentrations of the pro/anti-inflammatory cytokines at the local and peripheral levels, synthesized by T-lymphocytes and macrophages is a crucial immunopathogenetic factor in the development of immune-depended infertility in patients with varicocele.

Keywords: varicocele, varicocelectomy, infertility, immunophenotyping, cytokines
p. 662-673 of the original issue
References
  1. Shiraishi K, Takihara H, Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis. World J Urol. 2010 Jun;28(3):359-64. doi: 10.1007/s00345-009-0462-5
  2. Shiraishi K, Matsuyama H, Takihara H. Pathophysiology of varicocele in male infertility in the era of assisted reproductive technology. Int J Urol. 2012 Jun;19(6):538-50. doi: 10.1111/j.1442-2042.2012.02982.x
  3. Majzoub A, Esteves S, Gosálvez J, Agarwal A. Specialized sperm function tests in varicocele and the future of andrology laboratory. Asian J Androl. 2016 Mar-Apr:18(2):205. doi: 10.4103/1008-682X.172642
  4. Pastuszak AW, Wang R. Varicocele and testicular function. Asian J Androl. 2015 Jul-Aug;17(4):659-67. doi: 10.4103/1008-682X.153539
  5. Fraczek M, Kurpisz M. Cytokines in the male reproductive tract and their role in infertility disorders. J Reprod Immunol. 2015 Apr;108:98-104. doi: 10.1016/j.jri.2015.02.001
  6. Bozhedomov VA, Lipatova NA, Alexeev RA, Alexandrova LM, Nikolaeva MA, Sukhikh GT. The role of the antisperm antibodies in male infertility assessment after microsurgical varicocelectomy. Andrology. 2014 Nov;2(6):847-55. doi: 10.1111/j.2047-2927.2014.00254.x
  7. Sarkar O, Bahrainwala J, Chandrasekaran S, Kothari S, Mathur PP, Agarwal A. Impact of inflammation on male fertility. Front Biosci (Elite Ed). 2011 Jan 1;3:89-95. doi: 10.2741/e223
  8. Golab J, Jakobisiak M, Lasek W, Stoklosa T. Immunologia (nowe wydanie). Warszawa: Wydawnictwo Naukowe PWN; 2015. 498 ð.
  9. Agarwal A, Prabakaran S, Allamaneni SS. Relationship between oxidative stress, varicocele and infertility: a meta-analysis. Reprod Biomed Online. 2006 May;12(5):630-33. doi: 10.1016/S1472-6483(10)61190-X
  10. Moretti E, Collodel G, Mazzi L, Campagna M, Iacoponi F, Figura N. Resistin, interleukin-6, tumor necrosis factor-alpha, and human semen parameters in the presence of leukocytospermia, smoking habit, and varicocele. Fertil Steril. 2014 Aug;102(2):354-60. doi: 10.1016/j.fertnstert.2014.04.017
  11. Jarazo-Dietrich S, Jacobo P, Pérez CV, Guazzone VA, Lustig L, Theas MS. Up regulation of nitric oxide synthase-nitric oxide system in the testis of rats undergoing autoimmune orchitis. Immunobiology. 2012 Aug;217(8):778-87. doi: 10.1016/j.imbio.2012.04.007
  12. Wang H, Lv Y, Hu K, Feng T, Jin Y, Wang Y, Huang Y, Chen B. Seminal plasma leptin and spermatozoon apoptosis in patients with varicocele and leucocytospermia. Andrologia. 2015 Aug;47(6):655-61. doi: 10.1111/and.12313
  13. Duan YG, Yu CF, Novak N, Bieber T, Zhu CH, Schuppe HC, Haidl G, Allam JP. Immunodeviation towards a Th17 immune response associated with testicular damage in azoospermic men. Int J Androl. 2011 Dec;34(6 Pt 2):e536-45. doi: 10.1111/j.1365-2605.2010.01137.x
  14. Havrylyuk A, Chopyak V, Kril I, Kurpisz M. The types of populations and subpopulations of t-lymphocytes in peripheral blood of men with disturbances their fertility function. ²munolog³ia ta Alergolog³ia: Nauka ³ Praktika. 2014;(1):14-26. http://nbuv.gov.ua/UJRN/Ita_2014_1_4 (In Ukr.)
  15. Jacobo P, Pérez CV, Theas MS, Guazzone VA, Lustig L. CD4+ and CD8+ T cells producing Th1 and Th17 cytokines are involved in the pathogenesis of autoimmune orchitis. Reproduction. 2011 Feb;141(2):249-58. doi: 10.1530/REP-10-0362
  16. Moretti E, Cosci I, Spreafico A, Serchi T, Cuppone AM, Collodel G. Semen characteristics and inflammatory mediators in infertile men with different clinical diagnoses. Int J Androl. 2009 Dec;32(6):637-46. doi: 10.1111/j.1365-2605.2008.00911.x
Address for correspondence:
79010, Ukraine,
Lviv, Pekarskaya Str., 69,
Danylo Halytsky Lviv National
Medical University,
Department of Urology
Of the Post-Graduate Education Faculty.
Tel. mobile +38 097 633-57-27,
e-mail: nyosyf@ukr.net,
Yosyf A. Nakonechnyi
Information about the authors:
Nakonechnyi Yosyf A., Post-Graduate Student of the Department of Urology of the Post-Graduate Education Faculty, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
https://orcid.org/0000-0002-6872-1889
Havrylyuk Anna M., MD, Associate Professor of the Department of Clinical Immunology and Allergology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
http://orcid.org/0000-0001-9808-8896
Nakonechnyi Andrii I., MD, Professor of the Pediatric Surgery Department, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
http://orcid.org/0000-0003-1402-6642
Chopyak Valentyna V., MD, Professor, Head of the Department of Clinical Immunology and Allergology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
http://orcid.org/0000-0003-3127-2028
Kurpisz Maciej M., MD, Professor, Head of the Department of Immunobiology, Reproduction and Stem Cells, Institute of Human Genetics Polish Academy of Sciences, Poznan, Republic of Poland.
http://orcid.org/0000-0003-3275-3245
Contacts | ©Vitebsk State Medical University, 2007-2023