Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Interleukin-1 superfamily genes expression in normal or impaired human spermatogenesis

Genes & Immunity volume 8, pages 100–107 (2007)Cite this article

Abstract

Interleukin-1 (IL-1) is a pleiotropic cytokine that may play a role in contributing to the specific immune environment of mammalian testis and in regulating cell differentiation. We have determined the transcription activity of the IL-1 gene family (using real-time polymerase chain reaction (PCR)) in two main functional testicular compartments (interstitial and intratubular ones), and in tissue homogenates obtained from patients with fertility disorders (spermatogenic arrest and testicular tumors). We observed the prominent expression of gene coding for IL-1 receptor antagonist (IL-1RA) in a purified fraction of gametogenic cells (normal gonad). Caspase-1 (ICE – IL-1β-converting enzyme) was highly expressed (on mRNA level) in interstitial compartments as well in testicular tumors (immune enhancement?). In addition we found, that the activity of IL-1RA gene decreased along spermatogenic alteration in an inversely related manner with IL-1α (from normal gonad through spermatogenic arrest to Sertoli cell only syndrome). Therefore, the quotient value of IL-1α/IL-1RA could potentially serve as the diagnostic molecular probe for spermatogenesis assessment. The precise level of mRNA for IL-1–IL-18 cytokines and their receptors, and specifically of the receptor antagonist in immune privileged gonad, could be one of the main factors responsible for maintaining testicular homeostasis, thus enabling generation of the mature spermatozoa.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Holstein AF, Schulze W, Davidoff M . Understanding spermatogenesis is a prerequisite for treatment. Reprod Biol Endocrinol 2003; 1: 107–123.

    Article  Google Scholar 

  2. Fiszer D, Ulbrecht M, Fernandez N, Johnson JP, Weiss EH, Kurpisz M . Analysis of HLA class Ib gene expression in male gametogenic cells. Eur J Immunol 1997; 27: 1691–1695.

    Article  CAS  Google Scholar 

  3. Hedger MP, Meinhardt A . Cytokines and the immune-testicular axis. J Reprod Immunol 2003; 58: 1–26.

    Article  CAS  Google Scholar 

  4. Dinarello CA . IL-1β. In: Oppenheim JJ, Feldman M (eds). Cytokine Reference. Academic Press: San Diego, 2001, pp 351–374.

    Google Scholar 

  5. Dinarello CA . IL-1α. In: Oppenheim JJ, Feldman M (eds). Cytokine Reference. Academic Press: San Diego, 2001, pp 307–318.

    Google Scholar 

  6. O'Neill LAJ, Dower SK . IL-1 receptor family. In: Oppenheim JJ, Feldman M (eds). Cytokine Reference. Academic Press: San Diego, 2001, pp 1565–1585.

    Google Scholar 

  7. Wilson KP, Black JA, Thomson JA, Kim EE, Griffith JP, Navia MA et al. Structure and mechanism of interleukin-1 beta converting enzyme. Nature 1994; 370: 270–275.

    Article  CAS  Google Scholar 

  8. Pollock AS, Turck J, Lovett DH . The prodomain of interleukin 1alpha interacts with elements of the RNA processing apparatus and induces apoptosis in malignant cells. FASEB J 2003; 17: 203–213.

    Article  CAS  Google Scholar 

  9. Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y et al. IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci USA 2003; 100: 2645–2650.

    Article  CAS  Google Scholar 

  10. Pollanen P, Soder O, Parvinen M . Interleukin-1 alpha stimulation of spermatogonial proliferation in vivo. Reprod Fertil Dev 1989; 1: 85–87.

    Article  CAS  Google Scholar 

  11. Petersen C, Boitani C, Froysa B, Soder O . Interleukin-1 is a potent growth factor for immature rat sertoli cells. Mol Cell Endocrinol 2002; 186: 37–47.

    Article  CAS  Google Scholar 

  12. Sultana T, Svechnikov KV, Gustafsson K, Wahlgren A, Tham E, Weber G et al. Molecular identity, expression and functional analysis of interleukin-1alpha and its isoforms in rat testis. Asian J Androl 2004; 6: 149–153.

    CAS  PubMed  Google Scholar 

  13. Svechnikov KV, Sultana T, Soder O . Age-dependent stimulation of Leydig cell steroidogenesis by interleukin-1 isoforms. Mol Cell Endocrinol 2001; 182: 193–201.

    Article  CAS  Google Scholar 

  14. Soder O, Sultana T, Jonsson C, Wahlgren A, Petersen C, Holst M . The interleukin-1 system in the testis. Andrologia 2000; 32: 52–55.

    CAS  PubMed  Google Scholar 

  15. Soder O, Syed V, Callard GV, Toppari J, Pollanen P, Parvinen M et al. Production and secretion of an interleukin-1-like factor is stage-dependent and correlates with spermatogonial DNA synthesis in the rat seminiferous epithelium. Int J Androl 1991; 14: 223–231.

    Article  CAS  Google Scholar 

  16. Janitz M, Fiszer D, Lukaszyk A, Skorupski W, Kurpisz M . Analysis of mRNA expression for interleukin-1 genes on human testicular cells. Immunol Lett 1995; 48: 139–143.

    Article  CAS  Google Scholar 

  17. Svechnikov K, Stocco DM, Soder O . Interleukin-1alpha stimulates steroidogenic acute regulatory protein expression via p38 MAP kinase in immature rat Leydig cells. J Mol Endocrinol 2003; 30: 59–67.

    Article  CAS  Google Scholar 

  18. Francavilla S, D'Abrizio P, Rucci N, Silvano G, Properzi G, Straface E et al. Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis. J Clin Endocrinol Metab 2000; 85: 2692–2700.

    Article  CAS  Google Scholar 

  19. Miwa K, Asano M, Horai R, Iwakura Y, Nagata S, Suda T . Caspase 1-independent IL-1beta release and inflammation induced by the apoptosis inducer Fas ligand. Nat Med 1998; 4: 1287–1292.

    Article  CAS  Google Scholar 

  20. Hedger MP . Macrophages and the immune responsiveness of the testis. J Reprod Immunol 2002; 57: 19–34.

    Article  CAS  Google Scholar 

  21. Fiszer D, Rozwadowska N, Lukaszyk A, Slomski R, Kurpisz M . Quantitative mRNA analysis of IL-1 gene system in human testis. Am J Reprod Immunol 2003; 50: 389–398.

    Article  CAS  Google Scholar 

  22. Gustafsson K, Sultana T, Zetterstrom CK, Setchell BP, Siddiqui A, Weber G . Production and secretion of interleukin-1alpha proteins by rat testis. Biochem Biophys Res Commun 2002; 297: 492–497.

    Article  CAS  Google Scholar 

  23. Rozwadowska N, Fiszer D, Kurpisz M . Interleukin-1 system in testis – quantitative analysis. Expression of immunomodulatory genes in male gonad. Adv Exp Med Biol 2001; 495: 177–180.

    Article  CAS  Google Scholar 

  24. Haugen TB, Landmark BF, Josefsen GM, Hansson V, Hogset A . The mature form of interleukin-1 alpha is constitutively expressed in immature male germ cells from rat. Mol Cell Endocrinol 1994; 105: R19–R23.

    Article  CAS  Google Scholar 

  25. Stevenson FT, Turck J, Locksley RM, Lovett DH . The N-terminal propiece of interleukin 1 alpha is a transforming nuclear oncoprotein. Proc Natl Acad Sci USA 1997; 94: 508–513.

    Article  CAS  Google Scholar 

  26. Fantuzzi G . Lessons from interleukin-deficient mice: the interleukin-1 system. Acta Physiol Scand 2001; 173: 5–9.

    Article  CAS  Google Scholar 

  27. Song GJ, Lee H, Park Y, Lee HJ, Lee YS, Seo JT et al. Expression pattern of germ cell-specific genes in the testis of patients with nonobstructive azoospermia: usefulness as a molecular marker to predict the presence of testicular sperm. Fertil Steril 2000; 73: 1104–1108.

    Article  CAS  Google Scholar 

  28. Rozwadowska N, Fiszer D, Kurpisz M . Function of the interleukin-1 gene system in immunomodulation, apoptosis and proliferation in the male gonad. Post Hig Med Dosw (Online) 2005; 59: 56–67.

    Google Scholar 

  29. Hussein MR, Abou-Deif ES, Bedaiwy MA, Said TM . MustafaPhenotypic characterization of the immune and mast cell infiltrates in the human testis shows normal and abnormal spermatogenesis. Fertil Steril 2005; 83: 1447–1453.

    Article  Google Scholar 

  30. Pantschenko AG, Pushkar I, Anderson KH, Wang Y, Miller LJ, Kurtzman SH et al. The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression. Int J Oncol 2003; 23: 269–284.

    CAS  PubMed  Google Scholar 

  31. Yang YM, Ramadani M, Huang YT . Overexpression of Caspase-1 in adenocarcinoma of pancreas and chronic pancreatitis. World J Gastroenterol 2003; 9: 2828–2831.

    Article  CAS  Google Scholar 

  32. Ricote M, Garcia-Tunon I, Bethencourt FR, Fraile B, Paniagua R, Royuela M . Interleukin-1 (IL-1alpha and IL-1beta) and its receptors (IL-1RI, IL-1RII, and IL-1Ra) in prostate carcinoma. Cancer 2004; 100: 1388–1396.

    Article  CAS  Google Scholar 

  33. Tsai WC, Tsai ST, Ko JY, Jin YT, Li C, Huang W et al. The mRNA profile of genes in betel quid chewing oral cancer patients. Oral Oncol 2004; 40: 418–426.

    Article  CAS  Google Scholar 

  34. Ramadani M, Gansauge F, Schlosser S, Yang Y, Beger HG, Gansauge S . Overexpression of caspase-1 in pancreatic disorders: implications for a function besides apoptosis. J Gastrointest Surg 2001; 5: 352–358.

    Article  CAS  Google Scholar 

  35. Strand ML, Wahlgren A, Svechnikov K, Zetterstrom C, Setchell BP, Soder O . Interleukin-18 is expressed in rat testis and may promote germ cell growth. Mol Cell Endocrinol 2005; 240: 64–73.

    Article  CAS  Google Scholar 

  36. Janitz M, Fiszer D, Michalczak-Janitz K, Lukaszyk A, Fernandez N, Skorupski W et al. Analysis of mRNA for class I HLA on human gametogenic cells. Mol Reprod Dev 1994; 38: 231–237.

    Article  CAS  Google Scholar 

  37. Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162: 156–159.

    Article  CAS  Google Scholar 

  38. Yin JL, Shackel NA, Zekry A, McGuinness PH, Richards C, Putten KV et al. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for measurement of cytokine and growth factor mRNA expression with fluorogenic probes or SYBR Green I. Immunol Cell Biol 2001; 79: 213–221.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by Committee for Scientific Research of Poland.

Author information

Authors and Affiliations

  1. Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland

    N Rozwadowska, D Fiszer & M Kurpisz

  2. Department of Infertility and Reproductive Endocrinology, Poznan University of Medical Sciences, Poznan, Poland

    P Jedrzejczak

  3. Department of Urology, District Regional Hospital of Poznan, Poznan, Poland

    W Kosicki

Authors
  1. N Rozwadowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Fiszer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Jedrzejczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W Kosicki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Kurpisz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Kurpisz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rozwadowska, N., Fiszer, D., Jedrzejczak, P. et al. Interleukin-1 superfamily genes expression in normal or impaired human spermatogenesis. Genes Immun 8, 100–107 (2007). https://doi.org/10.1038/sj.gene.6364356

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364356

Keywords

This article is cited by

Search

Advanced search

Quick links