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Hamid Tahtamouni, L., Nael Hamdan, M., Ali Al-Mazaydeh, Z., Mahmoud Bawadi, R., Sobhi Rammaha, M., Mohammad Zghoul, A., Ahmad Ahram, M., & Refat Yasin, S. (2020). Alu-repeat polymorphism in the tissue plasminogen activator (t-PA) gene, seminal t-PA concentration, and male fertility impairment: A case-control study. International Journal of Reproductive BioMedicine (IJRM), 13(8), 571–578. https://doi.org/10.18502/ijrm.v13i8.7496
https://doi.org/10.18502/ijrm.v13i8.7496
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authors
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Lubna Hamid Tahtamouni
Lubna Hamid Tahtamouni
Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan
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Mahmoud Nael Hamdan
Mahmoud Nael Hamdan
Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan
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Zainab Ali Al-Mazaydeh
Zainab Ali Al-Mazaydeh
Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan
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Randa Mahmoud Bawadi
Randa Mahmoud Bawadi
Department of Physiology and Biochemistry, School of Medicine, the University of Jordan, Amman, Jordan
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Majdoleen Sobhi Rammaha
Majdoleen Sobhi Rammaha
Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan
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Ahmad Mohammad Zghoul
Ahmad Mohammad Zghoul
Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan
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Mamoun Ahmad Ahram
Mamoun Ahmad Ahram
Department of Physiology and Biochemistry, School of Medicine, the University of Jordan, Amman, Jordan
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Salem Refat Yasin
Salem Refat Yasin
Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan
Published Date
- Aug 19, 2020
Alu-repeat polymorphism in the tissue plasminogen activator (t-PA) gene, seminal t-PA concentration, and male fertility impairment: A case-control study
Abstract
Background: Tissue plasminogen activator (t-PA) is a protein involved in the fibrinolytic system that catalyzes the conversion of plasminogen into the active plasmin. The activity of t-PA is controlled by plasminogen activator inhibitor-1. t-PA has crucial functions during spermatogenesis. One polymorphism was reported for t-PA gene, either the presence of a 300-bp Alu-repeat (Alu+) or its absence (Alu−).
Objective: The current work aimed at studying the association between Alu polymorphism in the t-PA gene and male infertility.
Materials and Methods: Using polymerase chain reaction on genomic DNA isolated from the blood of 79 participants, a region polymorphic for Alu element insertion in t-PA gene was amplified. In addition, total t-PA concentration, plasminogen activator inhibitor-1/t-PA complex concentration, and t-PA activity in seminal plasma were measured by enzyme-linked immunosorbent assay.
Results: The results indicate that the percentage of infertile participants (n = 50) who were homozygous for t-PA Alu insertion (Alu+/+), heterozygous Alu+/− or homozygous for t-PA Alu deletion (Alu−/−) did not change significantly (p = 0.43, 0.81, and 0.85, respectively) when compared with the control participants (n = 29). On the other hand, a significant decrease (p = 0.0001) of t-PA total concentration in seminal plasma was observed in the infertile group in comparison with the control group. However, the results indicate that there is no association between the t-PA Alu different genotypes and the total t-PA seminal concentration in the infertile group when compared to the control group (p = 0.63).
Conclusion: Data obtained from the current study does not support an association between t-PA Alu polymorphism and t-PA seminal concentration or male infertility.
Key words: Alu element, Male infertility, Semen, Spermatogenesis, t-PA.
References
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[11] Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci 2015; 8: 191–196.
[12] Dimitriadis F, Adonakis G, Kaponis A, Mamoulakis C, Takenaka A, Sofikitis N. Pre-testicular, testicular, and post-testicular causes of male infertility. In: Simoni M, Huhtaniemi I (eds). Endocrinology of the testis and male reproduction. Cham: Springer; 2017: 1–47.
[13] Griswold MD. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol 1998; 9: 411–416.
[14] Liu YX, Liu K, Zhou HM, Du Q, Hu ZY, Zou RJ. Hormonal regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 in cultured monkey Sertoli cells. Hum Reprod 1995; 10: 719–727.
[15] Zhang T, Zhou HM, Liu YX. Expression of plasminogen activator and inhibitor, urokinase receptor and inhibin subunits in rhesus monkey testes. Mol Hum Reprod 1997; 3: 223–231.
[16] Hrafnkelsdottir T, Gudnason T, Wall U, Jern C, Jern S. Regulation of local availability of active tissue−type plasminogen activator in vivo in man. J Thromb Haemost 2004; 2: 1960–1968.
[17] Collen D, Lijnen HR. The tissue-type plasminogen activator story. Arterioscler Thromb Vasc Boil 2009; 29: 1151–1155.
[18] Cesari M, Pahor M, Incalzi RA. Plasminogen activator inhibitor−1 (PAI−1): a key factor linking fibrinolysis and age−related subclinical and clinical conditions. Cardiovasc Ther 2010; 28: e72–e91.
[19] Ny T, Elgh F, Lund B. The structure of the human tissuetype plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. Proc Natl Acad Sci USA 1984; 81: 5355–5359.
[20] Yang-Feng TL, Opdenakker G, Volckaert G, Franke U. Human tissue-type plasminogen activator gene located near chromosomal breakpoint in myeloproliferative disorder. Am J Hum Genet 1986; 39: 79–87.
[21] Ludwig M, Wohn KD, Schleuning WD, Olek K. Allelic dimorphism in the human tissue-type plasminogen activator (TPA) gene as a result of an Alu insertion/deletion event. Hum Genet 1992; 88: 388–392.
[22] Jern C, Ladenvall P, Wall U, Jern S. Gene polymorphism of t-PA is associated with forearm vascular release rate of t-PA. Arterioscler Thromb Vasc Boil 1999; 19: 454–459.
[23] Chandler WL, Levy WC, Stratton JR. The circulatory regulation of TPA and UPA secretion, clearance, and inhibition during exercise and during the infusion of isoproterenol and phenylephrine. Circulation 1995; 92: 2984–2994.
[24] Bourdon V, Defamie N, Fenichel P, Pointis G. Regulation of tissue-type plasminogen activator and its inhibitor (PAI- 1) by lipopolysaccharide-induced phagocytosis in a Sertoli cell line. Exp Cell Res 1999; 247: 367–372.
[25] Guo J, Shi YQ, Yang W, Li YC, Hu ZY, Liu YX. Testosterone upregulation of tissue type plasminogen activator expression in Sertoli cells. Endocrine 2007; 32: 83–89.
[26] Liu YX. Involvement of plasminogen activator and plasminogen activator inhibitor type 1 in spermatogenesis, sperm capacitation, and fertilization. Semin Thromb Hemost 2007; 33: 29–40.
[27] World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th Ed. Switzerland: World Health Organization; 2010.
[28] Hamdi HK, Reznik J, Castellon R, Atilano SR, Ong JM, Udar N, et al. Alu DNA polymorphism in ACE gene is protective for age-related macular degeneration. Biochem Biophys Res Comm 2002; 295: 668–672.
[29] Valle-Garay E, Montes AH, Corte JR, Meana A, Fierer J, Asensi V. tPA Alu (I/D) polymorphism associates with bacterial osteomyelitis. J Infect Dis 2013; 208: 218–223.
[30] Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag 2006; 2: 213–219.
[31] Liu K, Liu YX, Du Q, Zhou HM, Lin X, Hu ZY, et al. Preliminary studies on the role of plasminogen activator in seminal plasma of human and rhesus monkey. Mol Hum Reprod 1996; 2: 99–104.
[32] Batzer MA, Deininger PL. Alu repeats and human genomic diversity. Nat Rev Genet 2002; 3: 370–379.
[33] van den Eijnden-Schrauwen Y, Lakenberg N, Emeis JJ, de Knijff P. Alu-repeat polymorphism in the tissue-type plasminogen activator (tPA) gene does not affect basal endothelial tPA synthesis. Thromb Haemost 1995, 74: 1202.
[34] Nikolopoulos GK, Bagos PG, Tsangaris I, Tsiara CG, Kopterides P, Vaiopoulos A, et al. The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI- 1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis. Clin Chem Lab Med 2014; 52: 937–950.
[2] Neto FT, Bach PV, Najari BB, Li PS, Goldstein M. Spermatogenesis in humans and its affecting factors. Semin Cell Dev Biol 2016; 59: 10–26.
[3] Walker WH. Testosterone signaling and the regulation of spermatogenesis. Spermatogenesis 2011; 1: 116–120.
[4] Sharpe R. Regulation of spermatogenesis. In: Knobil E, Neill JD (eds). The physiology of reproduction. New York: Raven Press; 1994: 1363–1434.
[5] Ramaswamy S, Marshall GR, Pohl CR, Friedman RL, Plant TM. Inhibitory and stimulatory regulation of testicular inhibin B secretion by luteinizing hormone and folliclestimulating hormone, respectively, in the rhesus monkey (Macaca mulatta). Endocrinology 2003; 144: 1175–1185.
[6] O’shaughnessy PJ, Monteiro A, Verhoeven G, De Gendt K, Abel MH. Effect of FSH on testicular morphology and spermatogenesis in gonadotrophindeficient hypogonadal mice lacking androgen receptors. Reproduction 2010; 139: 177–184.
[7] Abel MH, Widen A, Wang X, Huhtaniemi I, Pakarinen P, Kumar TR, et al. Pituitary gonadotrophic hormone synthesis, secretion, subunit gene expression and cell structure in normal and follicle−stimulating hormone β knockout, follicle−stimulating hormone receptor knockout, luteinising hormone receptor knockout, hypogonadal and ovariectomised female mice. J Neuroendocrinol 2014; 26: 785–795.
[8] Ramaswamy S, Weinbauer GF. Endocrine control of spermatogenesis: Role of FSH and LH/testosterone. Spermatogenesis 2015; 4: e996025.
[9] Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International committee for monitoring assisted reproductive technology, World Health Organization. The international committee for monitoring assisted reproductive technology (ICMART) and the world health organization (WHO) revised glossary on ART terminology, 2009. Hum Reprod 2009; 24: 2683–2687.
[10] Olayemi FO. A review on some causes of male infertility. Afr J Biotechnol 2010; 9: 2834–2842.
[11] Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: A review of literature. J Hum Reprod Sci 2015; 8: 191–196.
[12] Dimitriadis F, Adonakis G, Kaponis A, Mamoulakis C, Takenaka A, Sofikitis N. Pre-testicular, testicular, and post-testicular causes of male infertility. In: Simoni M, Huhtaniemi I (eds). Endocrinology of the testis and male reproduction. Cham: Springer; 2017: 1–47.
[13] Griswold MD. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol 1998; 9: 411–416.
[14] Liu YX, Liu K, Zhou HM, Du Q, Hu ZY, Zou RJ. Hormonal regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 in cultured monkey Sertoli cells. Hum Reprod 1995; 10: 719–727.
[15] Zhang T, Zhou HM, Liu YX. Expression of plasminogen activator and inhibitor, urokinase receptor and inhibin subunits in rhesus monkey testes. Mol Hum Reprod 1997; 3: 223–231.
[16] Hrafnkelsdottir T, Gudnason T, Wall U, Jern C, Jern S. Regulation of local availability of active tissue−type plasminogen activator in vivo in man. J Thromb Haemost 2004; 2: 1960–1968.
[17] Collen D, Lijnen HR. The tissue-type plasminogen activator story. Arterioscler Thromb Vasc Boil 2009; 29: 1151–1155.
[18] Cesari M, Pahor M, Incalzi RA. Plasminogen activator inhibitor−1 (PAI−1): a key factor linking fibrinolysis and age−related subclinical and clinical conditions. Cardiovasc Ther 2010; 28: e72–e91.
[19] Ny T, Elgh F, Lund B. The structure of the human tissuetype plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. Proc Natl Acad Sci USA 1984; 81: 5355–5359.
[20] Yang-Feng TL, Opdenakker G, Volckaert G, Franke U. Human tissue-type plasminogen activator gene located near chromosomal breakpoint in myeloproliferative disorder. Am J Hum Genet 1986; 39: 79–87.
[21] Ludwig M, Wohn KD, Schleuning WD, Olek K. Allelic dimorphism in the human tissue-type plasminogen activator (TPA) gene as a result of an Alu insertion/deletion event. Hum Genet 1992; 88: 388–392.
[22] Jern C, Ladenvall P, Wall U, Jern S. Gene polymorphism of t-PA is associated with forearm vascular release rate of t-PA. Arterioscler Thromb Vasc Boil 1999; 19: 454–459.
[23] Chandler WL, Levy WC, Stratton JR. The circulatory regulation of TPA and UPA secretion, clearance, and inhibition during exercise and during the infusion of isoproterenol and phenylephrine. Circulation 1995; 92: 2984–2994.
[24] Bourdon V, Defamie N, Fenichel P, Pointis G. Regulation of tissue-type plasminogen activator and its inhibitor (PAI- 1) by lipopolysaccharide-induced phagocytosis in a Sertoli cell line. Exp Cell Res 1999; 247: 367–372.
[25] Guo J, Shi YQ, Yang W, Li YC, Hu ZY, Liu YX. Testosterone upregulation of tissue type plasminogen activator expression in Sertoli cells. Endocrine 2007; 32: 83–89.
[26] Liu YX. Involvement of plasminogen activator and plasminogen activator inhibitor type 1 in spermatogenesis, sperm capacitation, and fertilization. Semin Thromb Hemost 2007; 33: 29–40.
[27] World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th Ed. Switzerland: World Health Organization; 2010.
[28] Hamdi HK, Reznik J, Castellon R, Atilano SR, Ong JM, Udar N, et al. Alu DNA polymorphism in ACE gene is protective for age-related macular degeneration. Biochem Biophys Res Comm 2002; 295: 668–672.
[29] Valle-Garay E, Montes AH, Corte JR, Meana A, Fierer J, Asensi V. tPA Alu (I/D) polymorphism associates with bacterial osteomyelitis. J Infect Dis 2013; 208: 218–223.
[30] Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag 2006; 2: 213–219.
[31] Liu K, Liu YX, Du Q, Zhou HM, Lin X, Hu ZY, et al. Preliminary studies on the role of plasminogen activator in seminal plasma of human and rhesus monkey. Mol Hum Reprod 1996; 2: 99–104.
[32] Batzer MA, Deininger PL. Alu repeats and human genomic diversity. Nat Rev Genet 2002; 3: 370–379.
[33] van den Eijnden-Schrauwen Y, Lakenberg N, Emeis JJ, de Knijff P. Alu-repeat polymorphism in the tissue-type plasminogen activator (tPA) gene does not affect basal endothelial tPA synthesis. Thromb Haemost 1995, 74: 1202.
[34] Nikolopoulos GK, Bagos PG, Tsangaris I, Tsiara CG, Kopterides P, Vaiopoulos A, et al. The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI- 1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis. Clin Chem Lab Med 2014; 52: 937–950.