Abstract
Recent studies have demonstrated that making the sorts of oxygen reactive, such as nitric oxide, can cause oxidative lipid damage, protein damage, and damage to the DNA of cells. Sperm DNA damage effect on the reduction of sperm mobility and damage of acrosome membrane lead to the inability of sperm to fertilize the oocyte. Increasing expression of endothelial nitric oxide synthase (eNOS) gene is seen in various diseases such as cardiovascular and infertility diseases. This study aimed to assess the association between eNOS gene single nucleotide polymorphism/SNP (rs2070744, T786C) and risk of male infertility and the quality of sperm parameters in an Iranian population. In this case-control study, 100 infertile men were enrolled as a patient group. Control groups consisted of 100 fertile men. T786C genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results showed that T786C SNP, contained frequent genotype TC (p = 0.000; OR = 0.000; 95% CI = 0.000–0.015), TC + CC genotypes (p = 0.000; OR = 0.000; 95% CI = 0.000–0.015), and C allele (p = 0.000; OR = 0.00; 95% CI = 0.000–0.007), revealed a significant with male infertility. Based on the findings of this study suggested that although T786C SNP could not be applied as an appropriate genetic risk factor for male infertility, it probably may be considered a protective marker for other researchers. However, more comprehensive studies in different populations are required to confirm our data.
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References
Agarwal A, Tvrda E, Sharma R (2014) Relationship amongst teratozoospermia, seminal oxidative stress and male infertility. Reprod Biol Endocrinol 12:45. https://doi.org/10.1186/1477-7827-12-45
Agarwal A, Roychoudhury S, Sharma R, Gupta S, Majzoub A, Sabanegh E (2017) Diagnostic application of oxidation-reduction potential assay for measurement of oxidative stress: clinical utility in male factor infertility. Reprod BioMed Online 34(1):48–57. https://doi.org/10.1016/j.rbmo.2016.10.008
Ambulkar PS, Sigh R, Reddy M, Varma PS, Gupta DO, Shende MR, Pal AK (2014) Genetic risk of azoospermia factor (AZF) microdeletions in idiopathic cases of azoospermia and oligozoospermia in central Indian population. J Clin Diagn Res 8(3):88–91. https://doi.org/10.7860/JCDR/2014/7680.4116
Antwi-Boasiako C, Dzudzor B, Kudzi W, Doku A, Dale CA, Sey F, Otu KH, Boatemaa GD, Ekem I, Ahenkorah J, Achel DG, Aboagye ET, Donkor ES (2018) Association between eNOS gene polymorphism (T786C and VNTR) and sickle cell disease patients in Ghana. Diseases 6(4):90. https://doi.org/10.3390/diseases6040090
Barbosa AM, Silva KSF, Lagares MH, Rodrigues DA, da Costa IR, Morais MP, Martins JVM, Mascarenhas RS, Campedelli FL, Moura K (2017) Atherosclerosis: analysis of the eNOS (T786C) gene polymorphism. Genet Mol Res 16(3). https://doi.org/10.4238/gmr16039708
Bianco BM, Ghirelli-Filho CM, Cavalheiro V, Cavalcanti C, Peluso MM, Gava S, Glina DM, Christofolini BCP (2013) Variants in endothelial nitric oxide synthase (eNOS) gene in idiopathic infertile Brazilian men. Gene 519(1):13–17. https://doi.org/10.1016/j.gene.2013.02.001
Chang J, Pan F, Tang Q, Wu W, Chen M, Lu C, Ding H, Hu L, Chen D, Xia Y, Wang X (2017) eNOS gene T786C, G894T and 4a4b polymorphisms and male infertility susceptibility: a meta-analysis. Andrologia 49(4). https://doi.org/10.1111/and.12646
Chari MG, Colagar AH (2011) Seminal plasma lipid peroxidation, total antioxidant capacity, and cigarette smoking in asthenoteratospermic men. J Men's Health 8(1):43–49. https://doi.org/10.1016/j.jomh.2010.09.230
Colagar AH, Souraki OA (2012) Review of pumpkin anticancer effects. Quran Med 1(4):77–88. https://doi.org/10.5812/quranmed.8923
Colagar AH, Jorsaraee GA, Marzony ET (2007) Cigarette smoking and the risk of male infertility. Pak J Biol Sci 10(21):3870–3874. https://doi.org/10.3923/pjbs.2007.3870.3874
Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM (2010) World Health Organization reference values for human semen characteristics. Hum Reprod Update 16(3):231–245. https://doi.org/10.1093/humupd/dmp048
Damario MA (2014) General aspects of fertility and infertility. Methods Mol Biol 1154:3–23. https://doi.org/10.1007/978-1-4939-0659-8_1
Fasel NJ, Wesseling C, Fernandez AA, Vallat A, Glauser G, Helfenstein F, Richner H (2017) Alternative reproductive tactics, sperm mobility and oxidative stress in Carollia perspicillata (Seba’s short-tailed bat). Behav Ecol Sociobiol 71: 11. https://doi.org/10.1007/s00265-016-2251-7
Faure C, Leveille P, Dupont C, Julia C, Chavatte-Palmer P, Sutton A, Levy R (2014) Are superoxide dismutase 2 and nitric oxide synthase polymorphisms associated with idiopathic infertility? Antioxid Redox Signal 21(4):565–569. https://doi.org/10.1089/ars.2014.5831
Ferlin A, Raicu F, Gatta V, Zuccarello D, Palka G, Foresta C (2007) Male infertility: role of genetic background. Reprod BioMed Online 14(6):734–745. https://doi.org/10.1016/s1472-6483(10)60677-3
Forstermann U, Closs EI, Pollock JS, Nakane M, Schwarz P, Gath I, Kleinert H (1994) Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions. Hypertension 23(6 Pt 2):1121–1131. https://doi.org/10.1161/01.hyp.23.6.1121
Fujisawa M, Yamanaka K, Tanaka H, Tanaka H, Okada H, Arakawa S, Kamidono S (2001) Expression of endothelial nitric oxide synthase in the Sertoli cells of men with infertility of various causes. BJU Int 87(1):85–88. https://doi.org/10.1046/j.1464-410x.2001.00986.x
Huang Q (2015) Genetic study of complex diseases in the post-GWAS era. J Genet Genomics 42(3):87–98. https://doi.org/10.1016/j.jgg.2015.02.001
Ioannidis JP, Ntzani EE, Trikalinos TA (2001) Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet 29(3):306–309. https://doi.org/10.1038/ng749
Josarayi GA, Mohammad-Hasani A, Aftabi A, Moudi E, Colagar AH (2017) The AhRR-c.565C>G transversion may increase total antioxidant capacity levels of the seminal plasma in infertile men. Environ Sci Pollut Res Int 24(21):17428–17435. https://doi.org/10.1007/s11356-017-9356-z
Khosronezhad N, Colagar AH, Jorsarayi SGA (2015) C26232T mutation in Nsun7 gene and reduce sperm motility in asthenoteratospermic men. J Genet Resour 1(1):25–30. https://doi.org/10.22080/jgr.2015.1118
Krausz C, Escamilla AR, Chianese C (2015) Genetics of male infertility: from research to clinic. Reproduction 150(5):R159–R174. https://doi.org/10.1530/rep-15-0261
Maćczak A, Cyrkler M, Bukowska B, Michałowicz J (2017) Bisphenol A, bisphenol S, bisphenol F and bisphenol AF induce different oxidative stress and damage in human red blood cells (in vitro study). Toxicol in Vitro 41:143–149. https://doi.org/10.1016/j.tiv.2017.02.018
Mäkelä S, Eklund R, Lähdetie J, Mikkola M, Hovatta O, Kere J (2005) Mutational analysis of the human SLC26A8 gene: exclusion as a candidate for male infertility due to primary spermatogenic failure. Mol Hum Reprod 11(2):129–132. https://doi.org/10.1093/molehr/gah140
Middendorff R, Muller D, Wichers S, Holstein AF, Davidoff MS (1997) Evidence for production and functional activity of nitric oxide in seminiferous tubules and blood vessels of the human testis. J Clin Endocrinol Metab 82(12):4154–4161. https://doi.org/10.1210/jcem.82.12.4432
Moghbelinejad S, Mozdarani H, Ghoraeian P, Asadi R (2018) Basic and clinical genetic studies on male infertility in Iran during 2000-2016: a review. Int J Reprod Biomed 17(3):131–148
Mostafa T, Rashed LA, Nabil N, Fouad H, Sabry D, El-Saied DM (2015) Endothelial nitric oxide synthase gene polymorphism relationship with semen parameters and oxidative stress in infertile oligoasthenoteratozoospermic men. Urology 85(5):1058–1061. https://doi.org/10.1016/j.urology.2015.01.023
Nadaud S, Bonnardeaux A, Lathrop M, Soubrier F (1994) Gene structure, polymorphism and mapping of the human endothelial nitric oxide synthase gene. Biochem Biophys Res Commun 198(3):1027–1033. https://doi.org/10.1006/bbrc.1994.1146
Pagliaro P (2003) Differential biological effects of products of nitric oxide (NO) synthase: it is not enough to say NO. Life Sci 73(17):2137–2149. https://doi.org/10.1016/s0024-3205(03)00593-9
Potts R, Newbury C, Smith G, Notarianni L, Jefferies T (1999) Sperm chromatin damage associated with male smoking. Mutat Res 423(1–2):103–111. https://doi.org/10.1016/s0027-5107(98)00242-5
Rajender S, Avery K, Agarwal A (2011) Epigenetics, spermatogenesis and male infertility. Mutat Res 727(3):62–71. https://doi.org/10.1016/j.mrrev.2011.04.002
Safarinejad MR, Shafiei N, Safarinejad S (2010) The role of endothelial nitric oxide synthase (eNOS) T-786C, G894T, and 4a/b gene polymorphisms in the risk of idiopathic male infertility. Mol Reprod Dev 77(8):720–727. https://doi.org/10.1002/mrd.21210
Saleh R, Agarwal A, Sharma R, Nelson D, Thomas AJ (2002) Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: a prospective study. Fertil Steril 78(3):491–499. https://doi.org/10.1016/S0015-0282(02)03294-6
Sansone A, Di Dato C, de Angelis C, Menafra D, Pozza C, Pivonello R, Isidori A, Gianfrilli D (2018) Smoke, alcohol and drug addiction and male fertility. Reprod Biol Endocrinol 16(1):3. https://doi.org/10.1186/s12958-018-0320-7
Song P, Zou S, Chen T, Chen J, Wang Y, Yang J, Song Z, Jiang H, Shi H, Huang Y, Li Z, Shi Y, Hu H (2015) Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis. Biol Reprod 92(2):38. https://doi.org/10.1095/biolreprod.114.123240
Sun XH, Zhu YY, Wang L, Liu HL, Ling Y, Li ZL, Sun LB (2017) The Catsper channel and its roles in male fertility: a systematic review. Reprod Biol Endocrinol 15(1):65. https://doi.org/10.1186/s12958-017-0281-2
Tsuji G, Takahara M, Uchi H, Matsuda T, Chiba T, Takeuchi S, Yasukawa F, Moroi Y, Furue M (2012) Identification of ketoconazole as an AhR-Nrf2 activator in cultured human keratinocytes: the basis of its anti-inflammatory effect. J Invest Dermatol 132(1):59–68. https://doi.org/10.1038/jid.2011.194
Yang X, Zhu D, Zhang H, Jiang Y, Hu X, Geng D, Wang R, Liu R (2018) Associations between DNAH1 gene polymorphisms and male infertility: a retrospective study. Medicine (Baltimore) 97(49):e13493. https://doi.org/10.1097/MD.0000000000013493
Ying HQ, Pu XY, Liu SR, ZC A (2013) Genetic variants of eNOS gene may modify the susceptibility to idiopathic male infertility. Biomarkers 18(5):412–417. https://doi.org/10.3109/1354750X.2013.805245
Yun YJ, Park JH, Song SH, Lee S (2008) The association of 4a4b polymorphism of endothelial nitric oxide synthase (eNOS) gene with the sperm morphology in Korean infertile men. Fertil Steril 90(4):1126–1131. https://doi.org/10.1016/j.fertnstert.2007.07.1382
Zhang SH, Zhang JH, Ding XP, Zhang S, Chen HH, Jing YL (2016) Association of polymorphisms in tektin-t gene with idiopathic asthenozoospermia in Sichuan, China. J Assist Reprod Genet 33(2):181–187. https://doi.org/10.1007/s10815-015-0617-9
Acknowledgments
We would like to thank Dr. Seyed Golam Ali Jorsaraei and Dr. Emadoddin Moudi, from Babol University of Medical Sciences (Babol Iran), Dr. Mohsen Asoori (Head of Pasteur Institute of Iran-Amol Research Center), and Ms. Masomeh Salehi-Doon (Mol & Cell Lab., University of Mazandaran, Iran) for some of the samples and any other supports. We are grateful to our colleagues for critical reviews of the manuscript.
Funding
This work was supported by the Islamic Azad University-Tonekabon Branch, dedicated to the MSc thesis of Faezeh Sadat Mousavi-Nasab (#IranDoc-1394-2040548).
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Mousavi-Nasab, F.S., Colagar, A.H. Investigation of the association of endothelial nitric oxide synthase (eNOS)-T786C gene polymorphism with the risk of male infertility in an Iranian population. Environ Sci Pollut Res 27, 22434–22440 (2020). https://doi.org/10.1007/s11356-020-08860-8
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DOI: https://doi.org/10.1007/s11356-020-08860-8