Clinical and Experimental Reproductive Medicine

  • 제47권1호
  • /
  • Pages.68-76
  • /
  • 2020
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지
DOI QR코드

DOI QR Code

The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

  • Hamidian, Saeideh (Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences) ;
  • Talebi, Ali Reza (Department of Anatomy, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences) ;
  • Fesahat, Farzaneh (Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences) ;
  • Bayat, Mohammad (Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences) ;
  • Mirjalili, Ali Mohammad (Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences) ;
  • Ashrafzadeh, Hamid Reza (Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences) ;
  • Rajabi, Mahya (Genetics Department of Biology, Yazd Science and Arts University) ;
  • Montazeri, Fateme (Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences) ;
  • Babaei, Saeid (Department of Anatomy, Faculty of Medicine, Arak University of Medical Sciences)
  • 투고 : 2019.07.22
  • 심사 : 2019.09.18
  • 발행 : 2020.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective: Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL. Methods: Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n = 20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment. Results: Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of PRM1, PRM2, and the PRM1/PRM2 ratio after treatment. Conclusion: Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.

키워드

참고문헌

  1. Zhu Y, Lu H, Huo Z, Ma Z, Dang J, Dang W, et al. MicroRNA-16 inhibits feto-maternal angiogenesis and causes recurrent spontaneous abortion by targeting vascular endothelial growth factor. Sci Rep 2016;6:35536. https://doi.org/10.1038/srep35536
  2. Lamont K, Scott NW, Jones GT, Bhattacharya S. Risk of recurrent stillbirth: systematic review and meta-analysis. BMJ 2015;350:h3080. https://doi.org/10.1136/bmj.h3080
  3. Cao X, Cui Y, Zhang X, Lou J, Zhou J, Wei R. The correlation of sperm morphology with unexplained recurrent spontaneous abortion: a systematic review and meta-analysis. Oncotarget 2017;8:55646-56. https://doi.org/10.18632/oncotarget.17233
  4. Zidi-Jrah I, Hajlaoui A, Mougou-Zerelli S, Kammoun M, Meniaoui I, Sallem A, et al. Relationship between sperm aneuploidy, sperm DNA integrity, chromatin packaging, traditional semen parameters, and recurrent pregnancy loss. Fertil Steril 2016;105:58-64. https://doi.org/10.1016/j.fertnstert.2015.09.041
  5. McQueen DB, Zhang J, Robins JC. Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and metaanalysis. Fertil Steril 2019;112:54-60. https://doi.org/10.1016/j.fertnstert.2019.03.003
  6. Corzett M, Mazrimas J, Balhorn R. Protamine 1: protamine 2 stoichiometry in the sperm of eutherian mammals. Mol Reprod Dev 2002;61:519-27. https://doi.org/10.1002/mrd.10105
  7. Carrell DT, Liu L. Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl 2001;22:604-10.
  8. Carrell DT, Emery BR, Hammoud S. Altered protamine expression and diminished spermatogenesis: what is the link? Hum Reprod Update 2007;13:313-27. https://doi.org/10.1093/humupd/dml057
  9. Venkatesh S, Kumar R, Deka D, Deecaraman M, Dada R. Analysis of sperm nuclear protein gene polymorphisms and DNA integrity in infertile men. Syst Biol Reprod Med 2011;57:124-32. https://doi.org/10.3109/19396368.2011.562960
  10. Nanassy L, Liu L, Griffin J, Carrell DT. The clinical utility of the protamine 1/protamine 2 ratio in sperm. Protein Pept Lett 2011;18:772-7. https://doi.org/10.2174/092986611795713934
  11. Aoki VW, Liu L, Carrell DT. Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males. Hum Reprod 2005;20:1298-306. https://doi.org/10.1093/humrep/deh798
  12. Steger K, Wilhelm J, Konrad L, Stalf T, Greb R, Diemer T, et al. Both protamine-1 to protamine-2 mRNA ratio and Bcl2 mRNA content in testicular spermatids and ejaculated spermatozoa discriminate between fertile and infertile men. Hum Reprod 2008;23:11-6. https://doi.org/10.1093/humrep/dem363
  13. Jiang W, Sun H, Zhang J, Zhou Q, Wu Q, Li T, et al. Polymorphisms in Protamine 1 and Protamine 2 predict the risk of male infertility: a meta-analysis. Sci Rep 2015;5:15300. https://doi.org/10.1038/srep15300
  14. Aoki VW, Christensen GL, Atkins JF, Carrell DT. Identification of novel polymorphisms in the nuclear protein genes and their relationship with human sperm protamine deficiency and severe male infertility. Fertil Steril 2006;86:1416-22. https://doi.org/10.1016/j.fertnstert.2006.04.033
  15. Hanzlikova J, Ulcova-Gallova Z, Malkusova I, Sefrna F, Panzner P. TH1-TH2 response and the atopy risk in patients with reproduction failure. Am J Reprod Immunol 2009;61:213-20. https://doi.org/10.1111/j.1600-0897.2009.00683.x
  16. Balhorn R, Reed S, Tanphaichitr N. Aberrant protamine 1/protamine 2 ratios in sperm of infertile human males. Experientia 1988;44:52-5. https://doi.org/10.1007/BF01960243
  17. Balhorn R, Corzett M, Mazrimas J, Watkins B. Identification of bull protamine disulfides. Biochemistry 1991;30:175-81. https://doi.org/10.1021/bi00215a026
  18. Agarwal A, Bui AD. Oxidation-reduction potential as a new marker for oxidative stress: correlation to male infertility. Investig Clin Urol 2017;58:385-99. https://doi.org/10.4111/icu.2017.58.6.385
  19. Pahune PP, Choudhari AR, Muley PA. The total antioxidant power of semen and its correlation with the fertility potential of human male subjects. J Clin Diagn Res 2013;7:991-5.
  20. Rafiee B, Morowvat MH, Rahimi-Ghalati N. Comparing the effectiveness of dietary vitamin C and exercise interventions on fertility parameters in normal obese men. Urol J 2016;13:2635-9.
  21. Sheweita SA, Tilmisany AM, Al-Sawaf H. Mechanisms of male infertility: role of antioxidants. Curr Drug Metab 2005;6:495-501. https://doi.org/10.2174/138920005774330594
  22. Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis 2016;22:463-93. https://doi.org/10.1111/odi.12446
  23. Aitken J, Fisher H. Reactive oxygen species generation and human spermatozoa: the balance of benefit and risk. Bioessays 1994;16:259-67. https://doi.org/10.1002/bies.950160409
  24. Gual-Frau J, Abad C, Amengual MJ, Hannaoui N, Checa MA, Ribas- Maynou J, et al. Oral antioxidant treatment partly improves integrity of human sperm DNA in infertile grade I varicocele patients. Hum Fertil (Camb) 2015;18:225-9. https://doi.org/10.3109/14647273.2015.1050462
  25. Menkveld R. Clinical significance of the low normal sperm morphology value as proposed in the fifth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen. Asian J Androl 2010;12:47-58. https://doi.org/10.1038/aja.2009.14
  26. Pullar JM, Carr AC, Bozonet SM, Rosengrave P, Kettle AJ, Vissers MC. Elevated seminal plasma myeloperoxidase is associated with a decreased sperm concentration in young men. Andrology 2017;5:431-8. https://doi.org/10.1111/andr.12327
  27. Ghasemzadeh J, Talebi AR, Khalili MA, Fesahat F, Halvaei I, Nabi A, et al. Sperm parameters, protamine deficiency, and apoptosis in total globozoospermia. Iran J Reprod Med 2015;13:495-502.
  28. Talebi AR, Ghasemzadeh J, Khalili MA, Halvaei I, Fesahat F. Sperm chromatin quality and DNA integrity in partial versus total globozoospermia. Andrologia 2018;50:e12823. https://doi.org/10.1111/and.12823
  29. Anbara H, Shahrooz R, Razi M, Malekinejad H, Najafi G. The effect of vitamin C on mice hemolytic anemia induced by phenylhydrazine: an animal model study using histological changes in testis, pre-implantation embryo development, and biochemical changes. Iran J Basic Med Sci 2018;21:668-77.
  30. Gil-Villa AM, Cardona-Maya W, Agarwal A, Sharma R, Cadavid A. Role of male factor in early recurrent embryo loss: do antioxidants have any effect? Fertil Steril 2009;92:565-71. https://doi.org/10.1016/j.fertnstert.2008.07.1715
  31. Ko EY, Sabanegh ES Jr. The role of over-the-counter supplements for the treatment of male infertility: fact or fiction? J Androl 2012;33:292-308. https://doi.org/10.2164/jandrol.111.013730
  32. Akmal M, Qadri JQ, Al-Waili NS, Thangal S, Haq A, Saloom KY. Improvement in human semen quality after oral supplementation of vitamin C. J Med Food 2006;9:440-2. https://doi.org/10.1089/jmf.2006.9.440
  33. Okon UA, Utuk II. Ascorbic acid treatment elevates follicle stimulating hormone and testosterone plasma levels and enhances sperm quality in albino Wistar rats. Niger Med J 2016;57:31-6. https://doi.org/10.4103/0300-1652.180570
  34. Patil PS, Humbarwadi RS, Patil AD, Gune AR. Immature germ cells in semen: correlation with total sperm count and sperm motility. J Cytol 2013;30:185-9. https://doi.org/10.4103/0970-9371.117682
  35. Rahiminia T, Yazd EF, Fesahat F, Moein MR, Mirjalili AM, Talebi AR. Sperm chromatin and DNA integrity, methyltransferase mRNA levels, and global DNA methylation in oligoasthenoteratozoospermia. Clin Exp Reprod Med 2018;45:17-24. https://doi.org/10.5653/cerm.2018.45.1.17
  36. Bianchi PG, Manicardi GC, Bizzaro D, Bianchi U, Sakkas D. Effect of deoxyribonucleic acid protamination on fluorochrome staining and in situ nick-translation of murine and human mature spermatozoa. Biol Reprod 1993;49:1083-8. https://doi.org/10.1095/biolreprod49.5.1083
  37. Iranpour FG, Nasr-Esfahani MH, Valojerdi MR, al-Taraihi TM. Chromomycin A3 staining as a useful tool for evaluation of male fertility. J Assist Reprod Genet 2000;17:60-6. https://doi.org/10.1023/A:1009406231811
  38. Deemeh MR, Tavalee M, Razavi S, Esfahani MH. Evaluation of protamine deficiency and DNA fragmentation in two globozoospermia patients undergoing ICSI. Int J Fertil Steril 2007;1:85-8.
  39. Ghasemnejad-Berenji M, Ghazi-Khansari M, Yazdani I, Nobakht M, Abdollahi A, Ghasemnejad-Berenji H, et al. Effect of metformin on germ cell-specific apoptosis, oxidative stress and epididymal sperm quality after testicular torsion/detorsion in rats. Andrologia 2018;50:e12846. https://doi.org/10.1111/and.12846
  40. Aoki VW, Moskovtsev SI, Willis J, Liu L, Mullen JB, Carrell DT. DNA integrity is compromised in protamine-deficient human sperm. J Androl 2005;26:741-8. https://doi.org/10.2164/jandrol.05063
  41. Halliwell B, Gutteridge JM. Free radicals in biology and medicine. Oxford: Oxford University Press; 2015.
  42. Khavarimehr M, Nejati V, Razi M, Najafi G. Ameliorative effect of omega-3 on spermatogenesis, testicular antioxidant status and preimplantation embryo development in streptozotocin-induced diabetes in rats. Int Urol Nephrol 2017;49:1545-60. https://doi.org/10.1007/s11255-017-1636-5
  43. Oosterhuis GJ, Mulder AB, Kalsbeek-Batenburg E, Lambalk CB, Schoemaker J, Vermes I. Measuring apoptosis in human spermatozoa: a biological assay for semen quality? Fertil Steril 2000;74:245-50. https://doi.org/10.1016/S0015-0282(00)00623-3
  44. Scott L. Pronuclear scoring as a predictor of embryo development. Reprod Biomed Online 2003;6:201-14. https://doi.org/10.1016/S1472-6483(10)61711-7
  45. Rogenhofer N, Ott J, Pilatz A, Wolf J, Thaler CJ, Windischbauer L, et al. Unexplained recurrent miscarriages are associated with an aberrant sperm protamine mRNA content. Hum Reprod 2017;32:1574-82. https://doi.org/10.1093/humrep/dex224
  46. Torregrosa N, Dominguez-Fandos D, Camejo MI, Shirley CR, Meistrich ML, Ballesca JL, et al. Protamine 2 precursors, protamine 1/protamine 2 ratio, DNA integrity and other sperm parameters in infertile patients. Hum Reprod 2006;21:2084-9. https://doi.org/10.1093/humrep/del114
  47. Tavalaee M, Razavi S, Nasr-Esfahani MH. Influence of sperm chromatin anomalies on assisted reproductive technology outcome. Fertil Steril 2009;91:1119-26. https://doi.org/10.1016/j.fertnstert.2008.01.063
  48. Mengual L, Ballesca JL, Ascaso C, Oliva R. Marked differences in protamine content and P1/P2 ratios in sperm cells from percoll fractions between patients and controls. J Androl 2003;24:438-47. https://doi.org/10.1002/j.1939-4640.2003.tb02692.x
  49. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol 2012;10:49. https://doi.org/10.1186/1477-7827-10-49
  50. Pasqualotto EB, Agarwal A, Sharma RK, Izzo VM, Pinotti JA, Joshi NJ, et al. Effect of oxidative stress in follicular fluid on the outcome of assisted reproductive procedures. Fertil Steril 2004;81:973-6. https://doi.org/10.1016/j.fertnstert.2003.11.021
  51. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl 2005;26:349-53. https://doi.org/10.2164/jandrol.04146
  52. Tremellen K. Treatment of sperm oxidative stress: a collaborative approach between clinician and embryologist. In: Henkel R, Samanta L, Agarwal A, eds. Oxidants, antioxidants and impact of the oxidative status in male reproduction. London: Academic Press; 2019. p. 225-35.
  53. Vani K, Kurakula M, Syed R, Alharbi K. Clinical relevance of vitamin C among lead-exposed infertile men. Genet Test Mol Biomarkers 2012;16:1001-6. https://doi.org/10.1089/gtmb.2012.0027
  54. Yun SJ, Bae GS, Park JH, Song TH, Choi A, Ryu BY, et al. Antioxidant effects of cultured wild ginseng root extracts on the male reproductive function of boars and guinea pigs. Anim Reprod Sci 2016;170:51-60. https://doi.org/10.1016/j.anireprosci.2016.04.002

피인용 문헌

  1. Evaluation of the association between polymorphisms of PRM1 and PRM2 and the risk of male infertility: a systematic review, meta-analysis, and meta-regression vol.10, pp.1, 2020, https://doi.org/10.1038/s41598-020-74233-3
  2. Vitamins as primary or adjunctive treatment in infertile men with varicocele: A systematic review vol.19, pp.3, 2020, https://doi.org/10.1080/2090598x.2021.1932124