Gelatinases and their tissue inhibitors are associated with oxidative stress: a potential set of markers connected with male infertility
Ewa M. Kratz A E , Anna Kałuża A , Mirosława Ferens-Sieczkowska A , Beata Olejnik A , Renata Fiutek B , Mariusz Zimmer C and Agnieszka Piwowar D
+ Author Affiliations
- Author Affiliations
A Department of Chemistry and Immunochemistry, Wrocław Medical University, O. Bujwida 44A, 50-345 Wrocław, Poland.
B Department of Laboratory Diagnostics, Wrocław Medical University, Academic Hospital, Borowska 213, 50-556 Wrocław, Poland.
C 2nd Department and Clinic of Gynaecology, Obstetrics and Neonatology, Wrocław Medical University, Academic Hospital, Borowska 213, 50-556 Wrocław, Poland.
D Department of Toxicology, Wrocław Medical University, Borowska 211, 50-556 Wrocław, Poland.
E Corresponding author. Email: ewa.kratz@umed.wroc.pl
Reproduction, Fertility and Development 28(7) 1029-1037 https://doi.org/10.1071/RD14268
Submitted: 22 March 2014 Accepted: 16 November 2014 Published: 7 January 2015
Abstract
The expression and activity of matrix metalloproteinases (MMPs) may be regulated by oxidative stress in various pathophysiological processes; therefore, the aim of the present study was to analyse the associations between the expression of the gelatinases MMP-9 and MMP-2 and their tissue inhibitors TIMP-1, TIMP-2 and levels of total antioxidant capacity (TAC) and advanced oxidation protein products (AOPP) in seminal plasma prepared for artificial insemination. Levels of MMPs and TIMPs were evaluated using ELISA, whereas TAC and AOPP in the seminal plasma of 131 childless men and 38 fertile volunteers were determined spectrophotometrically. Seminal MMP-9 expression was higher in childless men than in fertile subjects, whereas there was no significant differences in MMP-2 expression between the analysed seminal groups. TIMP-1 and TIMP-2 expression was similar in all groups. However, TAC expression was significantly higher in infertile normozoospermic and oligozoospermic men and AOPP expression was higher in astheno-, oligo- and normozoospermic infertile patients than in fertile men. High AOPP, together with an increased MMP-9 : TIMP-1 ratio alters the oxidative–antioxidative balance of the ejaculate, thereby reducing male fertility, and therefore these parameters may serve as additional diagnostic markers of semen quality and male reproductive potential.
Additional keywords: human seminal plasma.
References
Agarwal, A., and Allamaneni, S. S. (2011). Free radicals and male reproduction. J. Indian Med. Assoc. 109, 184–187.| 22010591PubMed |
Agarwal, A., Prabakaran, S., and Allamaneni, S. S. (2006). Relationship between oxidative stress, varicocele and infertility: a meta-analysis. Reprod. Biomed. Online 12, 630–633.
| Relationship between oxidative stress, varicocele and infertility: a meta-analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xltleitrk%3D&md5=09b7390804c01c1f996a50c6ad82f0cdCAS | 16790111PubMed |
Agarwal, A., Makker, K., and Sharma, R. (2008). Clinical relevance of oxidative stress in male factor infertility: an update. Am. J. Reprod. Immunol. 59, 2–11.
| Clinical relevance of oxidative stress in male factor infertility: an update.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXis1Wjsbc%3D&md5=d1b5458b2c2f48b175a6cce7e2b56a56CAS | 18154591PubMed |
Agarwal, A., Virk, G., Ong, C., and du Plessis, S. S. (2014). Effect of oxidative stress on male reproduction. World J. Mens Health 32, 1–17.
| Effect of oxidative stress on male reproduction.Crossref | GoogleScholarGoogle Scholar | 24872947PubMed |
Aitken, R. J., and Baker, M. A. (2013). Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development. Int. J. Dev. Biol. 57, 265–272.
| Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhsVersbnO&md5=90ae3d246c4a6781cc7f900b1d845109CAS | 23784837PubMed |
Aitken, R. J., and Curry, B. J. (2011). Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line. Antioxid. Redox Signal. 14, 367–381.
| Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht1SjsA%3D%3D&md5=9fc3d78a21b9a670aada29a805404d0aCAS | 20522002PubMed |
Aitken, R. J., Ryan, A. L., Curry, B. J., and Baker, M. A. (2003). Multiple forms of redox activity in populations of human spermatozoa. Mol. Hum. Reprod. 9, 645–661.
| Multiple forms of redox activity in populations of human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXosVeruro%3D&md5=b69a7a2d9a7f36305f8262ab836a5e57CAS | 14561808PubMed |
Aktan, G., Doğru-Abbasoğlu, S., Küçükgergin, C., Kadıoğlu, A., Ozdemirler-Erata, G., and Koçak-Toker, N. (2013). Mystery of idiopathic male infertility: is oxidative stress an actual risk? Fertil. Steril. 99, 1211–1215.
| Mystery of idiopathic male infertility: is oxidative stress an actual risk?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvVCrsr7K&md5=6123e2bc5001787fcabdb49c8211e18dCAS | 23254182PubMed |
Bagis, T., Haydardedeoglu, B., Kilicdag, E. B., Cok, T., Simsek, E., and Parlakgumus, A. H. (2010). Single versus double intrauterine insemination in multi-follicular ovarian hyperstimulation cycles: a randomized trial. Hum. Reprod. 25, 1684–1690.
| Single versus double intrauterine insemination in multi-follicular ovarian hyperstimulation cycles: a randomized trial.Crossref | GoogleScholarGoogle Scholar | 20457669PubMed |
Baumgart, E., Lenk, S. V., Loening, S. A., and Jung, K. (2002a). Quantitative differences in matrix metalloproteinase (MMP)-2, but not in MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 or TIMP-2, in seminal plasma of normozoospermic and azoospermic patients. Hum. Reprod. 17, 2919–2923.
| Quantitative differences in matrix metalloproteinase (MMP)-2, but not in MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 or TIMP-2, in seminal plasma of normozoospermic and azoospermic patients.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XptFOrurg%3D&md5=fffc2fd0b58da4ed3d9ccbaa5aaf08a6CAS | 12407049PubMed |
Baumgart, E., Lenk, S. V., Loening, S. A., and Jung, K. (2002b). Tissue inhibitors of metalloproteinases 1 and 2 in human seminal plasma and their association with spermatozoa. Int. J. Androl. 25, 369–371.
| Tissue inhibitors of metalloproteinases 1 and 2 in human seminal plasma and their association with spermatozoa.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XptlSmt7s%3D&md5=1803b31392d5f418a0ddbbe058f19a7eCAS | 12406369PubMed |
Benedetti, S., Tagliamonte, M. C., Catalani, S., Primiterra, M., Canestrari, F., De Stefani, S., Palini, S., and Bulletti, C. (2012). Differences in blood and semen oxidative status in fertile and infertile men, and their relationship with sperm quality. Reprod. Biomed. Online 25, 300–306.
| Differences in blood and semen oxidative status in fertile and infertile men, and their relationship with sperm quality.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhtlait73K&md5=f6c2dce5f468e1d45ae9cd572c1d73bfCAS | 22818093PubMed |
Benzie, I. F., and Strain, J. J. (1996). The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP assay. Anal. Biochem. 239, 70–76.
| The ferric reducing ability of plasma (FRAP) as a measure of ‘antioxidant power’: the FRAP assay.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XksFCmt7Y%3D&md5=276a7ec3a9f697005e53e1dcca37d36eCAS | 8660627PubMed |
Bogani, P., Canavesi, M., Hagen, T. M., Visioli, F., and Bellosta, S. (2007). Thiol supplementation inhibits metalloproteinase activity independent of glutathione status. Biochem. Biophys. Res. Commun. 363, 651–655.
| Thiol supplementation inhibits metalloproteinase activity independent of glutathione status.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtFCjtrzM&md5=8f4d502395e6b9efc4e97d03f9fcb2b9CAS | 17900531PubMed |
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254.
| A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE28XksVehtrY%3D&md5=84aec28e8a212c17872b05093c0cb556CAS | 942051PubMed |
Brenneisen, P., Wenk, J., Klotz, L. O., Wlaschek, M., Briviba, K., Krieg, T., Sies, H., and Scharffetter-Kochanek, K. (1998). Central role of ferrous/ferric iron in the ultraviolet B irradiation-mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloprotease (MMP)-1) and stromelysin-1 (MMP-3) mRNA levels in cultured human dermal fibroblasts. J. Biol. Chem. 273, 5279–5287.
| Central role of ferrous/ferric iron in the ultraviolet B irradiation-mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloprotease (MMP)-1) and stromelysin-1 (MMP-3) mRNA levels in cultured human dermal fibroblasts.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c7kvVSkuw%3D%3D&md5=bbb3b5babd47aae9ec4b101a4966bbb8CAS | 9478985PubMed |
Buchman-Shaked, O., Kraiem, Z., Gonen, Y., and Goldman, S. (2002). Presence of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinase in human sperm. J. Androl. 23, 702–708.
| 1:CAS:528:DC%2BD38Xns1Kntbw%3D&md5=1242ce386240ca26424b756907fa5fdbCAS | 12185105PubMed |
Cao, G., Sofic, E., and Prior, R. L. (1997). Antioxidant and prooxidant behavior of flavonoids: structure–activity relationships. Free Radic. Biol. Med. 22, 749–760.
| Antioxidant and prooxidant behavior of flavonoids: structure–activity relationships.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXos1yguw%3D%3D&md5=e8da88f36a647e125840e5c9369afb06CAS | 9119242PubMed |
de Lamirande, E., and Lamothe, G. (2010). Levels of semenogelin in human spermatozoa decrease during capacitation: involvement of reactive oxygen species and zinc. Hum. Reprod. 25, 1619–1630.
| Levels of semenogelin in human spermatozoa decrease during capacitation: involvement of reactive oxygen species and zinc.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVWmtb7M&md5=565aa2e98685cab51e42955f5bf527fcCAS | 20501468PubMed |
Galati, G., Sabzevari, O., Wilson, J. X., and O’Brien, P. J. (2002). Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics. Toxicology 177, 91–104.
| Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xlt1OksbY%3D&md5=c98225118407193dae6172179c2ecb45CAS | 12126798PubMed |
Gharagozloo, P., and Aitken, R. J. (2011). The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum. Reprod. 26, 1628–1640.
| The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy.Crossref | GoogleScholarGoogle Scholar | 21546386PubMed |
Mahfouz, R., Sharma, R., Sharma, D., Sabanegh, E., and Agarwal, A. (2009). Diagnostic value of the total antioxidant capacity (TAC) in human seminal plasma. Fertil. Steril. 91, 805–811.
| Diagnostic value of the total antioxidant capacity (TAC) in human seminal plasma.Crossref | GoogleScholarGoogle Scholar | 18314108PubMed |
Mahfouz, R., Sharma, R., Thiyagarajan, A., Kale, V., Gupta, S., Sabanegh, E., and Agarwal, A. (2010). Semen characteristics and sperm DNA fragmentation in infertile men with low and high levels of seminal reactive oxygen species. Fertil. Steril. 94, 2141–2146.
| Semen characteristics and sperm DNA fragmentation in infertile men with low and high levels of seminal reactive oxygen species.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlent7rE&md5=18f8ba1b4e7baf3e75e54c7d558a68c5CAS | 20117780PubMed |
Makker, K., Agarwal, A., and Sharma, R. (2009). Oxidative stress and male infertility. Indian J. Med. Res. 129, 357–367.
| 1:CAS:528:DC%2BD1MXovFSntr0%3D&md5=d9785ef8604aaead4ba9063bf7a25b24CAS | 19535829PubMed |
McCauley, T. C., Zhang, H. M., Bellin, M. E., and Ax, R. L. (2001). Identification of a heparin-binding protein in bovine seminal fluid as tissue inhibitor of metalloproteinases-2. Mol. Reprod. Dev. 58, 336–341.
| Identification of a heparin-binding protein in bovine seminal fluid as tissue inhibitor of metalloproteinases-2.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhtVShsrw%3D&md5=a9c47e742cb0711e2c01911fd8f44737CAS | 11170275PubMed |
Mehrotra, A., Katiyar, D. K., Agarwal, A., Das, V., and Pant, K. K. (2013). Role of total antioxidant capacity and lipid peroxidation in fertile and infertile men. Biomed. Res. 24, 347–352.
| 1:CAS:528:DC%2BC3sXhtFars7rE&md5=fff5b56e01c0c4daec2935daf613581cCAS |
Métayer, S., Dacheux, F., Dacheux, J. L., and Gatti, J. L. (2002). Comparison, characterization, and identification of proteases and protease inhibitors in epididymal fluids of domestic mammals. Matrix metalloproteinases are major fluid gelatinases. Biol. Reprod. 66, 1219–1229.
| Comparison, characterization, and identification of proteases and protease inhibitors in epididymal fluids of domestic mammals. Matrix metalloproteinases are major fluid gelatinases.Crossref | GoogleScholarGoogle Scholar | 11967181PubMed |
Mora-Esteves, C., and Shin, D. (2013). Nutrient supplementation: improving male fertility fourfold. Semin. Reprod. Med. 31, 293–300.
| Nutrient supplementation: improving male fertility fourfold.Crossref | GoogleScholarGoogle Scholar | 23775385PubMed |
Nagase, H., and Woessner, J. F. (1999). Matrix metalloproteinases. J. Biol. Chem. 274, 21 491–21 494.
| Matrix metalloproteinases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXltVynu7s%3D&md5=23971f89742e6e01cf1030c204e142c1CAS |
Nelson, K. K., and Melendez, J. A. (2004). Mitochondrial redox control of matrix metalloproteinases. Free Radic. Biol. Med. 37, 768–784.
| Mitochondrial redox control of matrix metalloproteinases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmsVGgsLc%3D&md5=6009e41a28cee69ede7190c6d0095205CAS | 15304253PubMed |
Owen, D. H., and Katz, D. F. (2005). A review of the physical and chemical properties of human semen and the formulation of a semen simulant. J. Androl. 26, 459–469.
| A review of the physical and chemical properties of human semen and the formulation of a semen simulant.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmtFKgur8%3D&md5=6cf8341600bb68119acdf3f69393cd5fCAS | 15955884PubMed |
Pahune, P. P., Choudhari, A. R., and Muley, P. A. (2013). The total antioxidant power of semen and its correlation with the fertility potential of human male subjects. J. Clin. Diagn. Res. 7, 991–995.
| The total antioxidant power of semen and its correlation with the fertility potential of human male subjects.Crossref | GoogleScholarGoogle Scholar | 23905087PubMed |
Pasqualotto, F. F., Sharma, R. K., Nelson, D. R., Thomas, A. J., and Agarwal, A. (2000). Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation. Fertil. Steril. 73, 459–464.
| Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c7ls1aqtg%3D%3D&md5=02cb86a62d8ce03434f0e705fb161a1aCAS | 10688996PubMed |
Robert, M., and Gagnon, C. (1999). Semenogelin I: a coagulum forming, multifunctional seminal vesicle protein. Cell. Mol. Life Sci. 55, 944–960.
| Semenogelin I: a coagulum forming, multifunctional seminal vesicle protein.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXkt1altbg%3D&md5=f5199c1003a7b632a6d3088a972eea62CAS | 10412373PubMed |
Saalu, L. C. (2010). The incriminating role of reactive oxygen species in idiopathic male infertility: an evidence based evaluation. Pak. J. Biol. Sci. 13, 413–422.
| The incriminating role of reactive oxygen species in idiopathic male infertility: an evidence based evaluation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1OlsrrP&md5=20525c2b8792b2eedd2017ee29d47d77CAS | 20973394PubMed |
Saengsoi, W., Shia, W. Y., Shyu, C. L., Wu, J. T., Warinrak, C., Lee, W. M., and Cheng, F. P. (2011). Detection of matrix metalloproteinase (MMP)-2 and MMP-9 in canine seminal plasma. Anim. Reprod. Sci. 127, 114–119.
| Detection of matrix metalloproteinase (MMP)-2 and MMP-9 in canine seminal plasma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFKis7jP&md5=7f968062fc3b66c821a806d4b93db2d6CAS | 21824735PubMed |
Saleh, R. A., Agarwal, A., Kandirali, E., Sharma, R. K., Thomas, A. J., Nada, E. A., Evenson, D. P., and Alvarez, J. G. (2002). Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa. Fertil. Steril. 78, 1215–1224.
| Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa.Crossref | GoogleScholarGoogle Scholar | 12477515PubMed |
Shimokawa, K., Katayama, M., Matsuda, Y., Takahashi, H., Hara, I., Sato, H., and Kaneko, S. (2002). Matrix metalloproteinase (MMP)-2 and MMP-9 activities in human seminal plasma. Mol. Hum. Reprod. 8, 32–36.
| Matrix metalloproteinase (MMP)-2 and MMP-9 activities in human seminal plasma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhsVWmsbY%3D&md5=db225489e74fecdf662ff26eb414f849CAS |
Shimokawa, K., Katayama, M., Matsuda, Y., Takahashi, H., Hara, I., and Sato, H. (2003). Complexes of gelatinases and tissue inhibitor of metalloproteinases in human seminal plasma. J. Androl. 24, 73–77.
| 1:CAS:528:DC%2BD3sXmt1GntLs%3D&md5=21ea05904f62aaf06f60832f0a37a506CAS | 12514086PubMed |
Showell, M. G., Brown, J., Yazdani, A., Stankiewicz, M. T., and Hart, R. J. (2011). Antioxidants for male subfertility. Cochrane Database Syst. Rev. 1, CD007411.
| 21249690PubMed |
Singh, P. P., Chandra, A., Mahdi, F., Roy, A., and Sharma, P. (2010). Reconvene and reconnect the antioxidant hypothesis in human health and disease. Indian J. Clin. Biochem 25, 225–243.
| Reconvene and reconnect the antioxidant hypothesis in human health and disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFGhurjL&md5=570b098dbc0721c9625b15d2357a4811CAS | 21731194PubMed |
Tentes, I., Asimakopoulos, B., Mourvati, E., Diedrich, K., Al-Hasani, S., and Nikolettos, N. (2007). Matrix metalloproteinase (MMP)-2 and MMP-9 in seminal plasma. J. Assist. Reprod. Genet. 24, 278–281.
| Matrix metalloproteinase (MMP)-2 and MMP-9 in seminal plasma.Crossref | GoogleScholarGoogle Scholar | 17616803PubMed |
Westermarck, J., and Kähäri, V. M. (1999). Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 13, 781–792.
| 1:CAS:528:DyaK1MXjtFGksrs%3D&md5=24ac06545cfad34aedbf8bf0d2abafa4CAS | 10224222PubMed |
World Health Organization (WHO). (2010). ‘WHO Laboratory Manual for the Examination and Processing of Human Semen.’ (WHO Press: Geneva.)
Witko-Sarsat, V., Friedlander, M., Capeillère-Blandin, C., Nguyen-Khoa, T., Nguyen, A. T., Zingraff, J., Jungers, P., and Descamps-Latscha, B. (1996). Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 49, 1304–1313.
| Advanced oxidation protein products as a novel marker of oxidative stress in uremia.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xkslagsbs%3D&md5=7a2888125cc6042d7faca2d771884507CAS | 8731095PubMed |
Wojtowicz-Praga, S. M., Dickson, R. B., and Hawkins, M. J. (1997). Matrix metalloproteinase inhibitors. Invest. New Drugs 15, 61–75.
| Matrix metalloproteinase inhibitors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXktlOls7s%3D&md5=e6ae25c559a7ab072259ce8311be121dCAS | 9195290PubMed |
Zini, A., San Gabriel, M., and Baazeem, A. (2009). Antioxidants and sperm DNA damage: a clinical perspective. J. Assist. Reprod. Genet. 26, 427–432.
| Antioxidants and sperm DNA damage: a clinical perspective.Crossref | GoogleScholarGoogle Scholar | 19768529PubMed |
