Skip to main content
Log in

Interleukin-1β, cyclooxygenase-2, and hypoxia-inducible factor-1α in asthenozoospermia

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Impaired male fertility may have a variety of causes, among which asthenozoospermia. In its etiology, several bioactive substances, such as cytokines may be involved. In this context, our aim was to evaluate the expression of interleukin-1β, cyclooxygenase-2, and hypoxia-inducible factor-1α, in spermatozoa isolated from normospermic fertile donors and asthenozoospermic infertile patients. We evaluated twenty-eight infertile patients affected by idiopathic asthenozoospermia and twenty-three normospermic fertile donors, age-matched. Sperm parameters were evaluated; immunohistochemical analysis and enzyme-linked immunosorbent assay were then performed in isolated spermatozoa. Spermatozoa from the asthenozoospermic group presented an increased expression of IL-1β, COX-2, and HIF-1α compared with the normospermic fertile subjects. Our results can lead us to speculate that the increased expression of these substances may influence sperm motility. Nevertheless, further studies are needed in order to assess whether these bioactive mediators have a potential relevance as targets in future therapeutic strategies for the treatment of male infertility.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Agarwal A, Saleh RA (2002) Role of oxidants in male infertility: rationale, significance and treatment. Urol Clin N Am 29:817–827

    Article  Google Scholar 

  • Aitken RJ, Best FS, Richardson DW, Djahanbakhch O, Mortimer D, Templeton AA, Lees MM (1982) An analysis of sperm function in cases of unexplained infertility: conventional criteria, movement characteristics, and fertilizing capacity. Fertil Steril 38:212–221

    PubMed  CAS  Google Scholar 

  • Buch JP, Kolon TF, Maulik N, Kreutzer DL, Das DK (1994) Cytokines stimulate lipid membrane peroxidation of human sperm. Fertil Steril 62:186–188

    PubMed  CAS  Google Scholar 

  • Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147

    PubMed  CAS  Google Scholar 

  • Harris RC, McKanna JA, Akai Y, Jacobson HR, Dubois RN, Breyer MD (1994) Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. J Clin Invest 94:2504–2510

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hellwig-Bürgel T, Stiehl DP, Wagner AE, Metzen E, Jelkmann W (2005) Review: hypoxia-inducible factor-1 (HIF-1): a novel transcription factor in immune reactions. J Interferon Cytokine Res 25:297–310

    Article  PubMed  Google Scholar 

  • Honorati MC, Cattini L, Facchini A (2004) IL-17, IL-1beta and TNF-alpha stimulate VEGF production by dedifferentiated chondrocytes. Osteoarthr Cartil 12:683–691

    Article  PubMed  Google Scholar 

  • Huleihel M, Levy A, Lunenfeld E, Horowitz S, Potashnik G, Glezerman M (1997) Distinct expression of cytokines and mitogenic inhibitory factors in semen of fertile and infertile men. Am J Reprod Immunol 37:304–309

    Article  PubMed  CAS  Google Scholar 

  • Huleihel M, Lunenfeld E, Horowitz S, Levy A, Potashnik G, Mazor M, Glezerman M (1999) Expression of IL-12, IL-10, PGE2, sIL-2R and sIL-6R in seminal plasma of fertile and infertile men. Andrologia 31:283–288

    Article  PubMed  CAS  Google Scholar 

  • Huleihel M, Lunenfeld E, Horowitz S, Levy A, Potashnik G, Glezerman M (2000) Production of interleukin-1-like molecules by human sperm cells. Fertil Steril 73:1132–1137

    Article  PubMed  CAS  Google Scholar 

  • Kirschenbaum A, Liotta DR, Yao S, Liu XH, Klausner AP, Unger P, Shapiro E, Leav I, Levine AC (2000) Immunohistochemical localization of cyclooxygenase-1 and cyclooxygenase-2 in the human fetal and adult male reproductive tracts. J Clin Endocrinol Metab 85:3436–3441

    PubMed  CAS  Google Scholar 

  • Lee TC, Ho HC (2011) Effects of prostaglandin E2 and vascular endothelial growth factor on sperm might lead to endometriosis-associated infertility. Fertil Steril 95:360–362. doi:10.1016/j.fertnstert.2010.08.040

    Article  PubMed  CAS  Google Scholar 

  • Lee JJ, Natsuizaka M, Ohashi S, Wong GS, Takaoka M, Michaylira CZ, Budo D, Tobias JW, Kanai M, Shirakawa Y, Naomoto Y, Klein-Szanto AJ, Haase VH, Nakagawa H (2010) Hypoxia activates the cyclooxygenase-2-prostaglandin E synthase axis. Carcinogenesis 31:427–434. doi:10.1093/carcin/bgp326

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Maslinska D, Kaliszek A, Opertowska J, Toborowicz J, Deregowski K, Szukiewicz D (1999) Constitutive expression of cyclooxygenase-2 (COX-2) in developing brain. A. Choroid plexus in human fetuses. Folia Neuropathol 37:287–291

    PubMed  CAS  Google Scholar 

  • McKanna JA, Zhang MZ, Wang JL, Cheng H, Harris RC (1998) Constitutive expression of cyclooxygenase-2 in rat vas deferens. Am J Physiol 275:R227–R233

    PubMed  CAS  Google Scholar 

  • Narko K, Ritvos O, Ristimäki A (1997) Induction of cyclooxygenase-2 and prostaglandin F2alpha receptor expression by interleukin-1beta in cultured human granulosa–luteal cells. Endocrinology 138:3638–3644

    PubMed  CAS  Google Scholar 

  • Perrotta I, Santoro M, Guido C, Avena P, Tripepi S, De Amicis F, Gervasi MC, Aquila S (2012) Expression of cyclooxygenase-1 (COX-1) and COX-2 in human male gametes from normal patients, and those with varicocele and diabetes: a potential molecular marker for diagnosing male infertility disorders. J Anat 221:209–220. doi:10.1111/j.1469-7580.2012.01534.x

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Rouzer CA, Marnett LJ (2009) Cyclooxygenases: structural and functional insights. J Lipid Res 50:S29–S34. doi:10.1194/jlr.R800042-JLR200

    Article  PubMed  PubMed Central  Google Scholar 

  • Salvolini E, Buldreghini E, Lucarini G, Vignini A, Di Primio R, Balercia G (2012) Nitric oxide synthase and tyrosine nitration in idiopathic asthenozoospermia: an immunohistochemical study. Fertil Steril 97:554–560. doi:10.1016/j.fertnstert.2011.12.022

    Article  PubMed  CAS  Google Scholar 

  • Salvolini E, Buldreghini E, Lucarini G, Vignini A, Lenzi A, Di Primio R, Balercia G (2013) Involvement of sperm plasma membrane and cytoskeletal proteins in human male infertility. Fertil Steril 99:697–704. doi:10.1016/j.fertnstert.2012.10.042

    Article  PubMed  CAS  Google Scholar 

  • Sanocka D, Jędrzejczak P, Szumala-Kąkol A, Frączek M, Kurpisz M (2003) Male genital tract inflammation: the role of selected interleukins in regulation of pro-oxidant and antioxidant enzymatic substances in seminal plasma. J Androl 24:448–455

    PubMed  Google Scholar 

  • Semenza GL (1999) Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Ann Rev Cell Dev Biol 15:551–578

    Article  CAS  Google Scholar 

  • Sharma RK, Agarwal A (1996) Role of reactive oxygen species in male infertility. Urology 48:835–850

    Article  PubMed  CAS  Google Scholar 

  • Skinner MK (1991) Cell-cell interactions in the testis. Endocr Rev 12:45–77

    Article  PubMed  CAS  Google Scholar 

  • Stanfield KM, Khan KN (2003) Localization of COX-2 in the male reproductive tract during sexual maturation. Inflammopharmacology 11:259–266

    Article  PubMed  CAS  Google Scholar 

  • Walch L, Morris PL (2002) Cyclooxygenase 2 pathway mediates IL-1beta regulation of IL-1alpha, -1beta, and IL-6 mRNA levels in Leydig cell progenitors. Endocrinology 143:3276–3283

    Article  PubMed  CAS  Google Scholar 

  • Wenger RH (2002) Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. FASEB J 16:1151–1162

    Article  PubMed  CAS  Google Scholar 

  • World Health Organization (2010) WHO Laboratory manual for the examination and processing of human semen, 5th edn. WHO Press, Geneva

    Google Scholar 

  • Yang F, Bleich D (2004) Transcriptional regulation of cyclooxygenase-2 gene in pancreatic beta-cells. J Biol Chem 279:35403–35411

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by PRIN 2009 grant n. FW5SP3_002 from Ministero dell’Istruzione, dell’ Università e della Ricerca, and by RSA grants from Università Politecnica delle Marche.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Laura Mazzanti.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salvolini, E., Buldreghini, E., Lucarini, G. et al. Interleukin-1β, cyclooxygenase-2, and hypoxia-inducible factor-1α in asthenozoospermia. Histochem Cell Biol 142, 569–575 (2014). https://doi.org/10.1007/s00418-014-1232-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-014-1232-z

Keywords

Navigation