LABORATORY DIAGNOSTICS OF MALE INFERTILITY. BIOMARKERS AND METHODS. Part II

Zh. Yu. Sapozhkova – MD, PhD, International Cytology School, Head, Senior Lecturer, Moscow Russia; Privat Medical Centre of Podolsk, Moscow Region, Head of Clinical Lab, doctor/cytologist, Podolsk, Moscow region, Russia.E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
G. A. Milovanova – Resident, Russian Medical Academy of Continuous Professional Education, Moscow, Russia.E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it..
O. I. Patsap – MD, PhD, Federal Center of Brain Research and Neurotechnologies FMBA, Moscow, Russia. E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it..

1. Hedger MP. (2015). The immunophysiology of male reproduction. Knobil Neill’s Physiol. Reprod. 2015, 805–892. DOI 10.1016/b978-0-12-397175-3.00019-3
2. Monika F, Sudhanshu B, and Meinhardt AA (2017). Immune Infertility-The Immune Privilege of the Testis. Berlin: Springer.
3. Mellor AL, and Munn DH (2006). Immune privilege: a recurrent theme in immunoregulation? Immunol. Rev. 213, 5–11. DOI 10.1111/j.1600-065x.2006.00443.x
4. Hedger MP. Immunophysiology and pathology of inflammation in the testis and epididymis. J Androl. 2011;32(6):625-640. doi:10.2164/jandrol.111.012989. DOI 10.1016/b978-0-12-397175-3.00019-3
5. Fijak M, Pilatz A, Hedger MP, et al. Infectious, inflammatory and 'autoimmune' male factor infertility: how do rodent models inform clinical practice?. Hum Reprod Update. 2018;24(4):416-441. DOI 10.1093/humupd/ dmy00
6. Philip J, Selvan D, Desmond AD. Mumps orchitis in the non-immune postpubertal male: a resurgent threat to male fertility?. BJU Int. 2006;97(1):138-141. DOI 10.1111/ j.1464-410X.2006.05902.x
7. Garolla A, Pizzol D, Bertoldo A, et al. Sperm viral infection and male infertility: focus on HBV, HCV, HIV, HPV, HSV, HCMV, and AAV. J Reprod Immunol. 2013;100(1):20-29. DOI 10.1016/j.jri.2013.03.004
8. Fallarino F, Luca G, Calvitti M, et al. Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone. J Exp Med. 2009;206(11):2511-2526. DOI 10.1084/jem.20090134
9. Zhao S, Zhu W, Xue S, Han D. Testicular defense systems: immune privilege and innate immunity. Cell Mol Immunol. 2014;11(5):428-437. DOI 10.1038/cmi.2014.38
10. De SK, Chen HL, Pace JL, et al. Expression of tumor necrosis factor-alpha in mouse spermatogenic cells. Endocrinology. 1993;133(1):389-396. DOI 10.1210/ endo.133.1.8319585
11. Avallet O, Vigier M, Leduque P, et al. Expression and regulation of transforming growth factor-beta 1 messenger ribonucleic acid and protein in cultured porcine Leydig and Sertoli cells. Endocrinology. 1994;134(5):2079-2087. DOI 10.1210/endo.134.5.8156908
12. Meehan T, Schlatt S, O?Bryan MK, et al. Regulation of germ cell and Sertoli cell development by activin, follistatin, and FSH. Dev Biol. 2000;220(2):225-237. DOI 10.1006/dbio.2000.9625
13. Gerdprasert O, O?Bryan MK, Muir JA, et al. The response of testicular leukocytes to lipopolysaccharide-induced inflammation: further evidence for heterogeneity of the testicular macrophage population. Cell Tissue Res. 2002;308(2):277-285. DOI 10.1007/s00441-002-0547-6
14. Bhushan S, Tchatalbachev S, Lu Y, et al. Differential activation of inflammatory pathways in testicular macrophages provides a rationale for their subdued inflammatory capacity. J Immunol. 2015;194(11):5455-5464. DOI 10.4049/ jimmunol.1401132
15. Mantovani A, Sica A, Sozzani S, et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677-686. DOI 10.1016/j.it.2004.09.015
16. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889-896. DOI 10.1038/ ni.1937
17. Geissmann F, Manz MG, Jung S, et al. Development of monocytes, macrophages, and dendritic cells [published correction appears in Science. 2010 Dec 3;330(6009):1319]. Science. 2010;327(5966):656-661. DOI 10.1126/science.1178331
18. Locati M, Mantovani A, Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv Immunol. 2013;120:163-184. DOI 10.1016/B978-0-12-417028-5.00006-5
19. Murray PJ, Allen JE, Biswas SK, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14-20. DOI 10.1016/j.immuni.2014.06.008
20. Li Y, Su Y, Zhou T, et al. Activation of the NLRP3 Inflammasome Pathway by Prokineticin 2 in Testicular Macrophages of Uropathogenic Escherichia coli- Induced Orchitis. Front Immunol. 2019;10:1872. Published 2019 Aug 14. DOI 10.3389/fimmu.2019.01872
21. Rival C, Lustig L, Iosub R, et al. Identification of a dendritic cell population in normal testis and in chronically inflamed testis of rats with autoimmune orchitis. Cell Tissue Res. 2006;324(2):311-318. DOI 10.1007/s00441-005-0129-5
22. Jacobo P, Guazzone VA, Jarazo-Dietrich S, et al. Differential changes in CD4+ and CD8+ effector and regulatory T lymphocyte subsets in the testis of rats undergoing autoimmune orchitis. J Reprod Immunol. 2009 Jul;81(1):44-54. DOI 10.1016/j.jri.2009.04.005. Epub 2009 Jun 10. PMID: 19520436.
23. Hedger MP, Meinhardt A. Local regulation of T cell numbers and lymphocyte-inhibiting activity in the interstitial tissue of the adult rat testis. J Reprod Immunol. 2000;48(2):69-80. DOI 10.1016/s0165-0378(00)00071-1
24. De Rose R, Fernandez CS, Hedger MP, et al. Characterisation of macaque testicular leucocyte populations and T-lymphocyte immunity. J Reprod Immunol. 2013;100(2):146-156. DOI 10.1016/j.jri.2013.09.003
25. Loveland KL, Klein B, Pueschl D, et al. Cytokines in Male Fertility and Reproductive Pathologies: Immunoregulation and Beyond. Front Endocrinol (Lausanne). 2017;8:307. Published 2017 Nov 20. DOI 10.3389/fendo. 2017.0030
26. T?ttelmann F, Nieschlag E. Nosologie andrologischer Krankheitsbilder. In: Nieschlag E, Behre HM, Nieschlag S (eds.): Andrologie – Grundlagen und Klinik der reproduktiven Gesundheit des Mannes. 3rd edition. Heidelberg: Springer 2009; 90–96.
27. Mazumdar S, Levine AS. Antisperm antibodies: etiology, pathogenesis, diagnosis, and treatment. Fertil Steril. 1998;70(5):799-810. DOI 10.1016/s0015-0282(98) 00302-1
28. Chamley LW, Clarke GN. Antisperm antibodies and conception. Semin Immunopathol. 2007;29(2):169-184. DOI 10.1007/s00281-007-0075-2
29. Ver?n GL, Molina RI, Tissera AD, et al. Incidence of Sperm Surface Autoantibodies and Relationship with Routine Semen Parameters and Sperm Kinematics. Am J Reprod Immunol. 2016;76(1):59-69. DOI 10.1111/ aji.12519
30. Weidner W, Pilatz A, Diemer T, et al. Male urogenital infections: impact of infection and inflammation on ejaculate parameters. World J Urol. 2013;31(4):717-723. DOI 10.1007/s00345-013-1082-7
31. WHO laboratory manual for the examination and processing of human semen. 5th edn. Geneva, 2010. 287 p. Available at: http://apps.who.int/iris/bitstream/10665/ 44261/1/ 9789241547789_eng.pdf
32. Sapozhkova ZhYu, Eremin KI. Updates in protocol for human semen examination. Russian Clinical Laboratory Diagnostics. 2020; 65 (2):106-110. DOI 10.18821/ 0869-2084-2020-65-2-106-110. (In Russ).
33. Sapozhkova Zh, Eremin K, Dolgov V. Unification of procedures of cytochemical staining of human ejaculate to determine the true fertility of men. Laboratornaya diagnostika. Vostochnaya Evropa. 2020, 9(1–2):41-49. DOI 10.34883/PI.2020.9.1.026. (In Russ).
34. Sapozhkova ZhYu. Patent on Invention. Method of Microscopic Diagnostics of Sperm Quality after Ejaculate Sedimentation. 2019 г ? 2 686685 http://new.fips.ru. (In Russ).
35. Sapozhkova ZhYu, Eremin KI. Patent on Invention. Method for combined measurement of concentration of peroxidase-positive cells (neutrophilic granulocytes) and sperm cells in human ejaculate using variations based on cytochemical staining. 2020 г ? 2 726207. (In Russ).
36. Weidner W, Wagenlehner FM, Marconi M, Pilatz A, Pantke KH, Diemer T. Acute bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: andrological implications. Andrologia. 2008;40(2):105-112. DOI 10.1007/s00345-013-1082-7
37. Schuppe HC, Pilatz A, Hossain H, et al. Urogenital Infection as a Risk Factor for Male Infertility. Dtsch Arztebl Int. 2017;114(19):339-346. DOI 10.3238/arztebl. 2017.0339
38. Clinical guidelines for andrology urology. Ed. by P.A. Scheplev. Moscow: Medforum, 2016. 120 p. (In Russ).
39. Sapozhkova ZhYu. VisionCyto? SpermSediment: New diagnostic possibilities of cytological examination of ejaculate sediment. Laboratory. Moscow, Labdiag. 2016, 1: 46. (In Russ).
40. Sapozhkova ZhJu, Shabalova IP, Kasojan KT. Issledovanie osadka jejakuljata v diagnostike infekcij, peredavaemyh polovym putem.: Uchebnoe posobie. M.: FGBOU DPO RMANPO MZ RF, 2017:27. ISBN 978-5-7249-2488-7. (In Russ).
41. Sapozhkova ZhJu, Makolin IA. OAO ?Medicina?, Shatalov Ju.N. NPCJeMP DZM Voprosy diagnostiki urogenital'nyh infekcij u muzhchin. Aktual'nye voprosy medicinskoi? praktiki: sbornik nauchnyh trudov. Vypusk 2. M.: OAO ?Medicina?, 2018: 58-61. (In Russ).
42. Sapozhkova Z, Kasoyan K, Kovalchuk E, Shabalova I. Sperm Sediment Cytology: A New Technique for Diagnosing Occult Urologic Infections. Acta Cytol. 2017;61(3):247-251. DOI 10.1159/000469653
43. Pochernikov DG, Postovoytenko NT, Strelnikov AI. Comparative analysis of cell culture and molecular genetic testing of semen microbiota in male infertility. Andrologiya i genital’naya khirurgiya = Andrology and Genital Surgery 2019;20(2):40–7. DOI 10.17650/2070-9781-2019-20-2-40-47
44. Gillan L, Evans G, Maxwell WM. Flow cytometric evaluation of sperm parameters in relation to fertility potential. Theriogenology. 2005;63(2):445-457. DOI 10.1016/j. theriogenology.2004.09.024
45. Henkel R, Kierspel E, Stalf T, et al. Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in non-leukocytospermic patients. Fertil Steril. 2005;83(3):635-642. DOI 10.1016/j.fertnstert. 2004.11.022
46. Erenpreiss J, Hlevicka S, Zalkalns J, Erenpreisa J. Effect of leukocytospermia on sperm DNA integrity: a negative effect in abnormal semen samples. J Androl. 2002;23(5):717-723.
47. Jashnani K, Gundawar R, Kavishwar V, Parameshwar V. Fine-Needle Aspiration Cytology of the Testes for the Classification of Azoospermia and Its Value in the Assessment of Male Infertility. Acta Cytol. 2020;64(3):216-223. DOI 10.1159/000502790
48. Schenck U, Schill WB. Cytology of the human seminiferous epithelium. Acta Cytol. 1988;32(5):689-696.
49. Papi? Z, Katona G, Skrabalo Z. The cytologic identification and quantification of testicular cell subtypes. Reproducibility and relation to histologic findings in the diagnosis of male infertility. Acta Cytol. 1988;32(5):697-706.
50. Foresta C, Varotto A, Scandellari C. Assessment of testicular cytology by fine needle aspiration as a diagnostic parameter in the evaluation of the azoospermic subject. Fertil Steril. 1992;57(4):858-865. DOI 10.1016/s0015-0282(16)54971-1