Suprunenko S. M.

LITERATURE REVIEWS

Scentific article

Oxidative stress of sperm (OSS) due to hyperproduction in seminal plasma of reactive oxygen species (ROS) (ozone, free radicals, hydrogen peroxide) is currently being considered among the most actively discussed causes of male infertility. Normally, ROS are present in the seminal plasma and act as physiological regulators of sperm function (activation of the acrosomal reaction, regulation of biochemical redox reactions of energy synthesis, elimination of biologically foreign proteins (exo- and endotoxins of microbes). Metabolic syndrome (MS) is now approximately equally common in men and women, and its incidence, for example, in the United States reaches 39%. In general, the problem of CU has acquired global significance today, as an increase in its frequency is observed in almost all developed countries. MS is a combination of abdominal obesity, insulin resistance (IR) or type 2 diabetes mellitus (DM-2), atherogenic dyslipidemia, hypertension, hemostasis disorders, endothelial dysfunction and chronic subclinical inflammation. According to most definitions, obesity and IR/ CD-2 are key components of MS. Decreased testosterone (androgen deficiency) is a new pathogenetically important component of MS in men, as the frequency and severity of androgen deficiency are directly proportional to obesity and impaired carbohydrate metabolism. Obesity is a key component of MS that has clear diagnostic criteria: with a European man’s waist circumference ≥ 94 cm, any specialist should diagnose «obesity», which has its code in ICD-10 (E.66). However, the negative contribution of obesity to the pathogenesis of male infertility is still clearly not appreciated in everyday clinical practice. The negative effect of obesity on testicular function is manifested in a decrease in total testosterone and sex-binding globulin, with adipose tissue hormones leptin, resistin and ghrelin play the most important role. Occurring in obesity androgen deficiency can lead to IP, which is a major metabolic factor that triggers systemic oxidative stress. P.M. Mah and G.A. Wittert cites similar evidence that obesity in men is significantly associated with low levels of total and free blood testosterone, which in turn increases the risk of developing both IR and diabetes-2. Today it is absolutely obvious that comprehensive diagnosis and pathogenetic therapy of male infertility is possible only with a team of specialists and these are the strict requirements of the XXI century – the century of pathogenetic and preventive medicine and interdisciplinary interactions. Therefore, a modern urologist from a surgeon must become a clinician and actively interact with related specialists (especially endocrinologists). Otherwise, the loss of reproductive potential by the male population may soon reach its «point of no return»…

metabolism, insulin resistance, infertility, obesity

1. Bozhedomov VA, Ushakova IV, Sporish YeA. Rol giperproduktsii aktivnykh form kisloroda v muzhskom besplodii i vozmozhnosti antioksidantnoy terapii (obzor literatury). Consilium Medicum. 2015;7:51-5. [in Russian].
2. Bozhedomov VA, Gromenko DS, Ushakov IV. Prichiny oksidativnogo stressa spermatozoidov. Probl reproduktsii. 2013;6:67-73. [in Russian].
3. Bozhedomov VA, Gromenko DS, Ushakov IV. Oksidativnyy stress spermatozoidov v patogeneze muzhskogo besplodiya. Urologiya. 2012;2:51-6. [in Russian].
4. Al‑Thakafi S, Al‑Hathal N. Disease Peyronie’s: a literature review on epidemiology, genetics, pathophysiology, diagnosis and work‑up. Transl Androl Urol. 2016;5(3):280-9.
5. Stuntz M, Perlaky A, des Vignes F, Kyriakides T, Glass D. The Prevalence of Peyronie’s Disease in the United States: A Population‑Based Study. PLoS One. 2016;11(2):32-7.
6. Villegas J, Schulz M, Soto L. Influence of reactive oxygen species produced by activated leukocytes at the level of apoptosis in mature human spermatozoa. Fertil Steril. 2015;83:808-10.
7. Zorn B, Vidmar G, Meden-Vrtovec H. Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm injection. Int J Androl. 2017;26:279-85.
8. Koppers AJ, Mitchell LA, Wang P. Phosphoinositide 3-kinase signalling pathway involvement in a truncated apoptotic cascade associated with motility loss and oxidative DNA damage in human spermatozoa. Biochem J. 2015;436:687-98.
9. Kemal Duru N, Morshedi M, Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril. 2017;74:1200-7.
10. Tremellen K. Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update. 2018;14:243-58.
11. Garrido N, Meseguer M, Alvarez J. Relationship among standard semen parameters, glutathione peroxidase glutathione reductase activity, and mRNA expression and reduced glutathione content in ejaculated spermatozoa from fertile and infertile men. Fertil Steril. 2014;82:1059-66.
12. Henkel R, Kierspel E, Stalf T. Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in nonleukocytospermic patients. Fertil Steril. 2015;83:635-42.
13. Sarkar O, Bahrainwala J, Chandrasekaran S. Impact of inflammation on male fertility. Front Biosci. 2011;3:89-95.
14. Eisenberg ML, Lipshultz LI. Varicocele-induced infertility: Newer insights into its pathophysiology. Indian J Urol. 2011;27:58-64.
15. Perez-Crespo M, Pintado B, Gutierrez-Adan A. Scrotal heat stress effects on sperm viability, sperm DNA integrity, and the offspring sex ratio in mice. Mol Reprod Dev. 2018;75:40-7.
16. WHO laboratory manual for the examination and processing of human semen. 5th ed., 2017. p. 142-6.
17. Alyayev YG, Allenov SN, Kulakova YeV. Stress i infertilnost: psikhologicheskiye aspekty besplodiya. Materialy IV Kongressa «Muzhskoye zdorovye». 2018. s. 198-9. [in Russian].
18. Bozhedomov VA, Gromenko DS, Ushakova IV. Prichiny oksidativnogo stressa spermatozoidov. Materialy IV Kongressa «Muzhskoye zdorovye». 2018. s. 209. [in Russian].
19. Makrushin GA, Kuznetsova NN, Shamin MV. Zavisimost fertilnykh svoystv eyakulyata ot urovnya leykospermii. Materialy VI Kongressa «Muzhskoye zdorovye». 2015. s. 205-6. [in Russian].
20. Gorbachinsky I, Akpinar, Assimos DG. Metabolic syndrome and urologic diseases. Rev Urol. 2010;12:157-80.
21. Knowler WC, Barrett-Connor E, Fowler SE. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2012;346:393-403.
22. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA. 2002;288:1723-7.
23. Geiss LS, Pan L, Cadwell B. Changes in incidence of diabetes in U.S. adults, 1997-2003. Am J Prev Med. 2016;30:371-7.
24. Kalyani RR, Dobs AS. Androgen deficiency, diabetes and the metabolic syndrome in men. Curr Opin Endocrinol Diabetes Obes. 2017;14:226-34.
25. Kupelian V, Hayes FJ, Link CL. Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab. 2018;93:3403-10.
26. Alberti G. Introduction to the metabolic syndrome. Eur Heart J. 2005;7(D):D3-5.
27. Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2019;2:231-7.
28. Dohle GR, Diemer T, Giwercman A. Male Infertility Guideline. EAU, 2012. p. 68.
29. Tyuzikov IA, Bazhina OV. Nekotoryye aspekty endokrinnogo besplodiya u muzhchin. Zaochnyye elektronnyye konferentsii RAYe. Dostupno: http://article\4728 [in Russian].
30. Tyuzikov IA. K voprosu o narushenii spermatogennoy funktsii yaichek. Sb. materialov Plenuma Rossiyskogo obshchestva urologov. Krasnodar: 2016. s. 217-8. [in Russian].
31. Tyuzikov IA. Skrytyye narusheniya metabolizma kak vozmozhnaya prichina muzhskoy infertilnosti. Aktualnyye voprosy urologii i andrologii: Sbornik materialov mezhdunarodnoy nauchnoprakticheskoy konferentsii, posvyashchennoy 100-letiyu kafedry urologii i andrologii SPbMAPO. SPb.: 2011. s. 227-30. [in Russian].
32. Tyuzikov IA. Vozmozhnosti metabolicheskoy terapii besplodiya u molodykh muzhchin s ozhireniyem. Materialy VII Vserossiyskogo kongressa «Muzhskoye zdorovye». Rostov-na-Donu: 2011. s. 288-90. [in Russian].
33. Gustafson B, Hammarstedt A, Andersson CX, Smith U. Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol. 2017;27(11):2276-83.
34. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2014;92(3):347-55.
35. Sanchez-Lara K, Morales-Graf L, Green D. Cancer and obesity. Gac Med Mex. 2015;146(5):326-31.
36. Roytberg GYe. Metabolicheskiy sindrom. MEDpress-inform; 2017. 224 s. [in Russian].
37. Lee MJ, Fried SK. Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion. Am J Physiol Endocrinol Metab. 2019;296(6):1230-8.
38. Kapoor D, Clarke S, Stanworth R. The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2017;156(5):595-602.
39. Svartberg J, von Möhlen D, Schirmer H. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study. Eur J Endocrinol. 2004;150(1):65-71.
40. Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2013;14(3):281-7.
41. Weinberg JM. Lipotoxicity. Kidney Int. 2006;70(9):1560-6.
42. Aitken RJ, Krausz C. Oxidative stress, DNA damage and the Y chromosome. Reproduction. 2011;122(4):497-506.
43. Nguyen RH, Wilcox AJ, Skaerven R, Baird DD. Mens body mass index and infertility. Hum Reprod. 2017;22(9):2488-93.
44. Ohwaki K, Endo F, Yano E. Relationship between body mass index and infertility in healthy male Japanese workers: a pilot study. Andrologia. 2019;41(2):100-4.
45. Bener A, Al-Ansari AA, Zirie M, Al-Hamaq AO. Is male fertility associated with type 2 diabetes mellitus. Int Urol Nephrol. 2019;41(4):777-84.
46. Stewart TM, Liu DY, Garrett C. Associations between andrological measures, hormones and semen quality in fertile Australian men: inverse relationship between obesity and sperm output. Hum Reprod. 2019;24(7):1561-8.
47. Chavarro JE, Toth TL, Wright DL. Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril. 2010;93(7):2222-31.
48. Hammoud AO, Wilde N, Gibson M. Male obesity and alteration in sperm parameters. Fertil Steril. 2018;90(6):222-5.
49. Kort HI, Massey JB, Elsner CW. Impact of body mass index values on sperm quantity and quality. J Androl. 2016;27(3):450-2.
50. Fejes I, Koloszár S, Szöllosi J. Is semen quality affected by male body fat distribution. Andrologia. 2015;37(5):155-9.
51. Ali ST, Shaikh RN, Siddiqi AN, Siddiqi PQ. Semen analysis in insulindependent/noninsulin-dependent diabetic men with/without neuropathy. Arch Androl. 1993;30(1):47-54.
52. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2013;26(5):1553-79.
53. Gilja I, Parazajder J, Radej M. Retrograde ejaculation and loss of emission: possibilities of conservative treatment. Eur Urol. 1994;25(3):2268.
54. el-Rufaie OE, Bener A, Abuzeid MS, Ali TA. Sexual dysfunction among type II diabetic men: a controlled study. J Psychosom Res. 1997;43(6):605-12.
55. El-Sakka AI. Premature ejaculation in non-insulin-dependent diabetic patients. Int J Androl. 2013;26(6):329-34.
56. Kasturi SS, Tannir J, Brannigan RE. The metabolic syndrome and male infertility. J Androl. 2018;29(3):251-9.
57. Tyuzikov IA, Grekov YeA. Novaya metabolicheskaya kontseptsiya patogeneza idiopaticheskogo muzhskogo besplodiya. Zdravookhr Tadzhikistana. 2011;3:392-4. [in Russian].
58. Tyuzikov IA. Sistemnaya metabolicheskaya terapiya muzhskogo besplodiya, assotsiirovannogo s ozhireniyem i insulinorezistentnostyu. Materialy Plenuma Rossiyskogo obshchestva urologov. Kislovodsk: 2011. s. 415-6. [in Russian].
59. Tyuzikov IA, Kalinchenko SYu, Martov AG. Rol korrektsii metabolicheskogo statusa pri reproduktivnykh narusheniyakh u muzhchin. Materialy X Vserossiyskogo Foruma s mezhdunarodnym uchastiyem «Muzhskoye zdorov’ye i dolgoletiye». M.: 2012. s. 95-6. [in Russian].
60. Shiraishi K, Takihara H, Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis. World J Urol. 2010;28(3):359-64.
61. Tsao CW, Hsu CY, Chou YC. The relationship between varicoceles and obesity in a young adult population. Int J Androl. 2019;32(4):38590.
62. Handel LN, Shetty R, Sigman M. The relationship between varicoceles and obesity. J Urol. 2016;176(5):2138-40.
63. Shafik A, Olfat S. Scrotal lipomatosis. Br J Urol. 1981;53(1):50-4.
64. Shafik A, Olfat S. Lipectomy in the treatment of scrotal lipomatosis. Br J Urol. 1981;53:55-61.
65. Brannian JD. Obesity and fertility. S D Med. 2011;64(7):251-4.
66. Goulis DG, Tarlatzis BC. Metabolic syndrome and reproduction: I. testicular function. Gynecol Endocrinol. 2018;24(1):33-9.
67. Pasquali R, Patton L, Gambineri A. Obesity and infertility. Curr Opin Endocrinol Diabetes Obes. 2017;14(6):482-7.
68. Mah PM, Wittert GA. Obesity and testicular function. Mol Cell Endocrinol. 2010;316(2):180-6.
69. Bernshteyn L. Antidiabeticheskikh biguanidami metformin i onkologicheskaya zabolevayemost. Sakh diabet. 2010;3:3-6. [in Russian].
70. Baron AD. Insulin resistance and vascular function. J Diabetes Complications. 2002;16(1):92-102.
71. Srikanthan P, Karlamangla AS. Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab. 2011;96(9):2898-903.
72. McVary KT, Rademaker A, Lloyd GL. Autonomic nervous system over activity in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol. 2015;1327-33.
73. Brüning JC, Gautam D, Burks DJ. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;2122-5.
74. Palmer NO, Bakos HW, Owens JA. Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. Am J Physiol Endocrinol Metab. 2012;302(7):768-80.
75. Sankhla M, Sharma TK, Mathur K. Relationship of oxidative stress with obesity and its role in obesity induced metabolic syndrome. Clin Lab. 2012;58(5-6):385-92.
76. La Vignera S, Condorelli R, Vicari E. Diabetes mellitus and sperm parameters. J Androl. 2012;33(2):145-53.
77. Yassin AA, Saad F, Gooren LJ. Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone. Andrologia. 2018;40(4):259-64.
78. Mallidis C, Czerwiec A, Filippi S. Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism. Reproduction. 2011;142(1):63-71.
79. Tyuzikov IA. Patologiya muzhskikh polovykh organov kak marker sakharnogo diabeta. Materialy Plenuma Rossiyskogo obshchestva urologov. Krasnodar: 2010. s. 292. [in Russian].
80. Tyuzikov IA, Kalinchenko SYu, Martov AG. Diagnosticheskoye i prognosticheskoye znacheniye neyropatii v protokole andrologicheskogo obsledovaniya. Materialy I Kongressa urologov Sibiri. Kemerovo: 2012. s. 325-8. [in Russian].
81. Morgante G, Tosti C, Orvieto R. Metformin improves semen characteristics of oligo-terato-asthenozoospermic men with metabolic syndrome. Fertil Steril. 2011;95(6):2150-2.
82. Tyuzikov IA. Insulinorezistentnost i muzhskoye besplodiye: diagnostika i vozmozhnosti medikamentoznoye korrektsii. Materialy Vserossiyskoy nauchno-prakticheskoy konferentsii s mezhdunarodnym uchastiyem «Ratsionalnaya farmakoterapiya v urologii 2011». M.: 2011. s. 148-9. [in Russian].
83. Tyuzikov IA. Idiopaticheskoy muzhskoye besplodiye: yestli «svet v kontse tunnelya» sovremennoy standartnoy diagnostiki Materialy Regionalnoy nauchnoy konferentsii «Muzhskoye zdorovye v Sibiri». Tomsk: 2011. s. 100-3. [in Russian].

«Bulletin of problems biology and medicine» Issue 3 (157), 2020 year, 35-40 pages, index UDK 616-008.9-06:616.697

10.29254/2077-4214-2020-3-157-35-40