Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Impact of Inflammation on Male Reproductive Tract

Authors
Department of Medical Laboratory Science, Faculty of Basic Medical Sciences, College of Medicine of the University of Lagos, Idi-Araba, Lagos, Nigeria
Abstract
Fertility in the male is dependent on the proper production of sperm cells. This process, called spermatogenesis is very complex and involves the synchronization of numerous factors. The presence of pro–inflammatory cytokines, tumor necrosis factor-alpha (TNF–α), interleukin–1 alpha (IL–1 α) and interleukin 1 beta (IL–1 β) cytokines in the male reproductive tract (testis, epididymis and sperm) may have certain physiological functions. However, when the levels of these cytokines are higher than normal, as seen in conditions of inflammation, they become very harmful to sperm production. Moreover, inflammation is also associated with oxidative stress and the latter is well known to impair sperm function. Epidemiological studies regarding male infertility have revealed that more and more infertile men suffer from acute or chronic inflammation of the genitourinary tract, which often occurs without any symptoms. The inflammatory reactions within the male genital tract are inevitably connected with oxidative stress. Oxidative stress, especially in sperm, is harmful because it damages sperm DNA and causes apoptosis in sperm. This article reviewed the suggested mechanisms and contribution of inflammation to male infertility. In addition, the review was further strengthened by discussing how inflammation affects both fertility and assisted reproductive technologies (ART).
Keywords

  1. Song N, Liu J, An S, Nishino T, Hishikawa Y, Koji T. Immunohistochemical Analysis of Histone H3 Modifications in Germ Cells during Mouse Spermatogenesis. Acta Histochem Cytochem. 2011;44(4):183-90.
  2. Sharlip ID, Jarow JP, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, et al. Best practice policies for male infertility. Fertil Steril. 2002;77(5):873-82.
  3. Belsey MA. The epidemiology of infertility: a review with particular reference to sub-Saharan Africa. Bull World Health Organ. 1976;54(3):319-41.
  4. Chukudebelu WO, Esege N, Megafu U. Etiological factors in infertility in Enugu, Nigeria. Infertility. 1979;2(2):193-200.
  5. Nwofor AME, Ugezu AI. The difficulties encountered in the management of male infertility in Nnewi, Nigeria. Niger Med J. 2003;45(1):56-9.
  6. Ikechebelu JI, Adinma JI, Orie EF, Ikegwuonu SO. High prevalence of male infertility in southeastern Nigeria. J Obstet Gynaecol. 2003;23(6):657-9.
  7. Poongothai J, Gopenath TS, Manonayaki S. Genetics of human male infertility. Singapore Med J. 2009;50(4):336-47.
  8. World Health Organisation. WHO Laboratory manual for the examination of human semen-cervical mucus interaction. 4th ed. Cambridge: Cambridge University Press; 1999. p. 1-86.
  9. Akinloye O, Arowojolu AO, Shittu OB, Anetor JI. Cadmium toxicity: a possible cause of male infertility in Nigeria. Reprod Biol. 2006;6(1):17-30.
  10. Akinloye O, Akintunde CO, Banjoko SO, Adaramoye AO, Adeleye AO. An assessment of the oestrogenic effect of soyprotein on female rabbits. Food Chem. 2002;77(1):67-9.
  11. Akinloye O, Arowojolu AO, Shittu OB, Adejuwon CA, Osotimehin B. Selenium status of idiopathic infertile Nigerian males. Biol Trace Elem Res. 2005;104(1):9-18.
  12. Akinloye O, Gromoll J, Callies C, Nieschlag E, Simoni M. Mutation analysis of the X-chromosome linked, testis-specific TAF7L gene in spermatogenic failure. Andrologia. 2007;39(5):190-5.
  13. Akinloye O, Gromoll J, Nieschlag E, Simoni M. Androgen receptor gene CAG and GGN polymorphisms in infertile Nigerian men. J Endocrinol Invest. 2009;32(10):797-804.
  14. Choudhury SR, Knapp LA. Human reproductive failure I: immunological factors. Hum Reprod Update. 2001;7(2):113-34.
  15. Oladokun A, Arulogun O, Oladokun R, Morhason-Bello IO, Bamgboye EA, Adewole IF, et al. Acceptability of child adoption as management option for infertility in Nigeria: evidence from focus group discussions. Afr J Reprod Health. 2009;13(1):79-91.
  16. Dhont N, van de Wijgert J, Luchters S, Muvunyi C, Vyankandondera J, Temmerman M. Sexual violence, HSV-2 and HIV are important predictors for infertility in Rwanda. Hum Reprod. 2010;25(10):2507-15.
  17. Dohle GR, Smit M, Weber RF. Androgens and male fertility. World J Urol. 2003;21(5):341-5.
  18. Mitchell RN, Cotran RS, editors. Acute and chronic inflammation. Philadelphia: Saunders Press; 2003. 33 p. (Kumar V, Cotran RS, Robbins SL, editors. Robbins Basic Pathology; vol. 127).
  19. DePalma AF, Rothman RH, Lewinnek GE, Canale ST. Anterior interbody fusion for severe cervical disc degeneration. Surg Gynecol Obstet. 1972;134(5):755-8.
  20. Purvis K, Christiansen E. Infection in the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility. Int J Androl. 1993;16(1):1-13.
  21. Comhaire FH, Mahmoud AM, Depuydt CE, Zalata AA, Christophe AB. Mechanisms and effects of male genital tract infection on sperm quality and fertilizing potential: the andrologist's viewpoint. Hum Reprod Update. 1999;5(5):393-8.
  22. Hales DB, Diemer T, Hales KH. Role of cytokines in testicular function. Endocrine. 1999;10(3):201-17.
  23. Soder O, Sultana T, Jonsson C, Wahlgren A, Petersen C, Holst M. The interleukin-1 system in the testis. Andrologia. 2000;32(1):52-5.
  24. Diemer T, Hales DB, Weidner W. Immune endocrine interactions and Leydig cell function: the role of cytokines. Andrologia. 2003;35(1):55-63.
  25. Maegawa M, Kamada M, Irahara M, Yamamoto S, Yoshikawa S, Kasai Y, et al. A repertoire of cytokines in human seminal plasma. J Reprod Immunol. 2002;54(1-2):33-42.
  26. Cudicini C, Lejeune H, Gomez E, Bosmans E, Ballet F, Saez J, et al. Human Leydig cells and Sertoli cells are producers of interleukins-1 and -6. J Clin Endocrinol Metab. 1997;82(5):1426-33.
  27. Male D, Brostoff J, Roth DB, Roit I. Mechanism of innate immunity in Immunology. 7th ed. Canada: Elsevier; 2006. 127 p.
  28. Keck C, Gerber-Schafer C, Clad A, Wilhelm C, Breckwoldt M. Seminal tract infections: impact on male fertility and treatment options. Hum Reprod Update. 1998;4(6):891-903.
  29. Potts JM, Sharma R, Pasqualotto F, Nelson D, Hall G, Agarwal A. Association of ureaplasma urealyticum with abnormal reactive oxygen species levels and absence of leukocytospermia. J Urol. 2000;163(6):1775-8.
  30. Warren JS, Johnson KJ, Ward PA. Oxygen radicals in cell injury and cell death. Pathol Immunopathol Res. 1987;6(5-6):301-15.
  31. Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79(4):829-43.
  32. Sharma RK, Said T, Agarwal A. Sperm DNA damage and its clinical relevance in assessing reproductive outcome. Asian J Androl. 2004;6(2):139-48.
  33. Sikka SC. Relative impact of oxidative stress on male reproductive function. Curr Med Chem. 2001;8(7):851-62.
  34. Naz RK, Evans L. Presence and modulation of interleukin-12 in seminal plasma of fertile and infertile men. J Androl. 1998;19(3):302-7.
  35. Gruschwitz MS, Brezinschek R, Brezinschek HP. Cytokine levels in the seminal plasma of infertile males. J Androl. 1996;17(2):158-63.
  36. Sanocka D, Jedrzejczak P, Szumała-Kaekol A, Fraczek M, Kurpisz M. Male genital tract inflammation: the role of selected interleukins in regulation of pro-oxidant and antioxidant enzymatic substances in seminal plasma. J Androl. 2003;24(3):448-55.
  37. Kocak I, Yenisey C, Dundar M, Okyay P, Serter M. Relationship between seminal plasma interleukin-6 and tumor necrosis factor alpha levels with semen parameters in fertile and infertile men. Urol Res. 2002;30(4):263-7.
  38. Shimoya K, Matsuzaki N, Tsutsui T, Taniguchi T, Saji F, Tanizawa O. Detection of interleukin-8 (IL-8) in seminal plasma and elevated IL-8 in seminal plasma of infertile patients with leukospermia. Fertil Steril. 1993;59(4):885-8.
  39. Depuydt CE, Bosmans E, Zalata A, Schoonjans F, Comhaire FH. The relation between reactive oxygen species and cytokines in andrological patients with or without male accessory gland infection. J Androl. 1996;17(6):699-707.
  40. Wolff H, Politch JA, Martinez A, Haimovici F, Hill JA, Anderson DJ. Leukocytospermia is associated with poor semen quality. Fertil Steril. 1990;53(3):528-36.
  41. Thomas J, Fishel SB, Hall JA, Green S, Newton TA, Thornton SJ. Increased polymorphonuclear granulocytes in seminal plasma in relation to sperm morphology. Hum Reprod. 1997;12(11):2418-21.
  42. Close CE, Roberts PL, Berger RE. Cigarettes, alcohol and marijuana are related to pyospermia in infertile men. J Urol. 1990;144(4):900-3.
  43. Blackwell JM, Zaneveld LJ. Effect of abstinence on sperm acrosin, hypoosmotic swelling, and other semen variables. Fertil Steril. 1992;58(4):798-802.
  44. Eggert-Kruse W, Kiefer I, Beck C, Demirakca T, Strowitzki T. Role for tumor necrosis factor alpha (TNF-alpha) and interleukin 1-beta (IL-1beta) determination in seminal plasma during infertility investigation. Fertil Steril. 2007;87(4):810-23.
  45. Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overview of the literature. Reprod Biomed Online. 2004;8(6):616-27.
  46. Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 2011;26(7):1628-40.
  47. Akinloye O, Abbiyesuku FM, Oguntibeju OO, Arowojolu AO, Truter EJ. The impact of blood and seminal plasma zinc and copper concentrations on spermogram and hormonal changes in infertile Nigerian men. Reprod Biol. 2011;11(2):83-98.
  48. Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol. 1997;82(2):291-5.
  49. Nakabeppu Y, Sakumi K, Sakamoto K, Tsuchimoto D, Tsuzuki T, Nakatsu Y. Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids. Biol Chem. 2006;387(4):373-9.
  50. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84.
  51. Stadtman ER. Protein oxidation and aging. Science. 1992;257(5074):1220-4.
  52. Twigg J, Fulton N, Gomez E, Irvine DS, Aitken RJ. Analysis of the impact of intracellular reactive oxygen species generation on the structural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants. Hum Reprod. 1998;13(6):1429-36.
  53. Aitken RJ, Baker MA, Sawyer D. Oxidative stress in the male germ line and its role in the aetiology of male infertility and genetic disease. Reprod Biomed Online. 2003;7(1):65-70.
  54. Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update. 2003;9(4):331-45.
  55. Sikka SC. Role of oxidative stress and antioxidants in andrology and assisted reproductive technology. J Androl. 2004;25(1):5-18.
  56. Agarwal A, Sekhon LH. The role of antioxidant therapy in the treatment of male infertility. Hum Fertil (Camb). 2010;13(4):217-25.
  57. Ursini F, Heim S, Kiess M, Maurine M, Roveri A, Wissing J, et al. Dual function of the selenoprotein PHGPx during sperm maturation. Science. 1999;285(5432):1393-6.
  58. Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil Steril. 1997;68(3):519-24.
  59. Carrell DT, Wilcox AL, Lowy L, Peterson CM, Jones KP, Erickson L, et al. Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss. Obstet Gynecol. 2003;101(6):1229-35.
  60. Steele EK, McClure N, Maxwell RJ, Lewis SE. A comparison of DNA damage in testicular and proximal epididymal spermatozoa in obstructive azoospermia. Mol Hum Reprod. 1999;5(9):831-5.