ارتباط بین DNA فراگمانتاسیون اسپرم و بیان RNA غیر کد کننده‌ی HOTAIR در مردان نابارور

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی کارشناسی ارشد، گروه علوم تشریحی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

2 دانشیار، گروه ژنتیک و بیولوژی مولکولی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

3 استاد، گروه علوم تشریحی، دانشکده‌ی پزشکی و مرکز باوری و ناباروری حضرت مریم (س)، بیمارستان شهید بهشتی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

چکیده

مقدمه: ناباروری، یک اختلال در سیستم تولید مثلی است که درصد قابل توجهی از علل آن مربوط به مردان می‌باشد. آسیب‌های وارده به DNA و عوامل ایجاد کننده‌ی آن، تأثیر منفی بر نتایج باروری در زوجین دارد. هدف از انجام مطالعه‌ی حاضر، ارزیابی حیات، DNA فراگمانتاسیون اسپرم و بیان ژن HOTAIR در مردان بارور و نابارور و بررسی ارتباط بین آن‌ها بود.روش‌ها: نمونه‌های مایع منی به صورت تصادفی از 25 مرد بارور و 25 مرد نابارور در محدوده‌ی سنی 55-25 سال که به مرکز باروری و ناباروری حضرت مریم (س) بیمارستان شهید بهشتی اصفهان مراجعه کرده بودند، جمع‌آوری گردید. ارزیابی حیات اسپرم‌ها با رنگ‌آمیزی ائوزین- نگروزین انجام شد. DNA فراگمانتاسیون با Sperm chromatin dispersion test (SCDT) اندازه‌گیری شد. برای اندازه‌گیری سطح بیان HOTAIR، از روش Real-time polymerase chain reaction (Real time-PCR) استفاده شد.یافته‌ها: میانگین بیان HOTAIR در افراد نابارور به طور معنی‌داری نسبت به گروه بارور کاهش یافت. سطح بیان HOTAIR با آسیب‌های DNA همبستگی منفی و با حیات اسپرم همبستگی مثبت معنی‌داری داشت (001/0 > P).نتیجه‌گیری: کاهش بیان HOTAIR و افزایش آسیب‌های DNA در افراد نابارور و همبستگی بین آن‌ها نشان از اهمیت ارزیابی آسیب DNA و تحقیقات پیرامون عوامل ایجاد کننده‌ی آن‌ها دارد.

کلیدواژه‌ها

عنوان مقاله [English]

The Correlation between Sperm DNA Fragmentation and the Expression of Long Non-Coding RNA HOTAIR in Infertile Men

نویسندگان [English]

  • Afsaneh Jaberi-Asl 1
  • Mohammadreza Sharifi 2
  • Gholam Reza Dashti 3
1 MSc Student, Department of Anatomy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Associate Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Professor, Department of Anatomical Sciences, School of Medicine AND Saint Maryam Fertility and Infertility Center, Shahid Beheshti Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
چکیده [English]

Background: Infertility is a disorder of the reproductive system that affects a significant percentage of men. DNA damage and its causative agents negatively affect fertility outcomes. The present study aimed to evaluate the sperm viability, DNA fragmentation, and HOTAIR gene expression in infertile and fertile men, and to investigate the correlation between them.Methods: Specimens of semen were obtained randomly from 25 fertile and 25 infertile men, aged between 25-55 years who were referred to Saint Maryam Fertility and Infertility Center of Shahid Beheshti Hospital, Isfahan, Iran. Sperm viability was assessed using Eosin-Nigrosin staining. DNA fragmentation was assessed by sperm chromatin dispersion test (SCDT). The expression of HOTAIR was detected using real-time polymerase chain reaction (real time-PCR).Findings: HOTAIR gene expression in infertile people was significantly decreased in comparison to fertile group. HOTAIR expression level was negatively correlated with DNA fragmentation and positively correlated with sperm viability (P < 0.001).Conclusion: Decreased HOTAIR expression and increased DNA damage in infertile people and the correlation between them indicating the importance of assessing DNA damage and research on their causative agents.

کلیدواژه‌ها [English]

  • Sperm
  • DNA
  • Long non-coding RNA
  • HOTAIR
  • Infertility

مراجع

  1. Oztekin U, Caniklioglu M, Sari S, Selmi V, Gurel A, Isikay L. Evaluation of male infertility prevalence with clinical outcomes in middle anatolian region. Cureus 2019; 11(7): e5122.
  2. Naz M, Kamal M. Classification, causes, diagnosis and treatment of male infertility: A review. Orient Pharm Exp Med 2017; 17(2): 89-109.
  3. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: Harms and benefits for human health. Oxid Med Cell Longev 2017; 2017: 8416763.
  4. Sadeghi Z, Shahla Ishaqi S, Dashti GR. The effect of folic acid and nicotinic acid on malondialdehyde levels of semen in oligospermia men after cryopreservation. J Isfahan Med Sch 2021; 38(603): 921-8. [In Persian].
  5. Toghiani S, Hayati RN, Dashti GR, Rouzbehani S. The effects of vitamin C and menthone on acyclovir induced DNA damage in rat spermatozoa: An experimental study. Int J Reprod Biomed 2018; 16(11): 703-10.
  6. Rui BR, Shibuya FY, Kawaoku AJT, Losano JDA, Angrimani DSR, Dalmazzo A, et al. Impact of induced levels of specific free radicals and malondialdehyde on chicken semen quality and fertility. Theriogenology 2017; 90: 11-9.
  7. Dorostghoal M, Kazeminejad SR, Shahbazian N, Pourmehdi M, Jabbari A. Oxidative stress status and sperm DNA fragmentation in fertile and infertile men. Andrologia 2017; 49(10).
  8. Zamani Rarani F, Golshan-Iranpour F, Dashti GR. Correlation between sperm motility and sperm chromatin/DNA damage before and after cryopreservation and the effect of folic acid and nicotinic acid on post-thaw sperm quality in normozoospermic men. Cell Tissue Bank 2019; 20(3): 367-78.
  9. Bhat SA, Ahmad SM, Mumtaz PT, Malik AA, Dar MA, Urwat U, et al. Long non-coding RNAs: Mechanism of action and functional utility. Noncoding RNA Res 2016; 1(1): 43-50.
  10. Marchese FP, Raimondi I, Huarte M. The multidimensional mechanisms of long noncoding RNA function. Genome Biol 2017; 18(1): 206.
  11. Li Q, Zhang J, Su DM, Guan LN, Mu WH, Yu M, et al. lncRNA TUG1 modulates proliferation, apoptosis, invasion, and angiogenesis via targeting miR-29b in trophoblast cells. Hum Genomics 2019; 13(1): 50.
  12. Sabet M, Sharifi M, Heidari M, Kazemi M, Babaei N. Blockage of HOTAIR reduced cell proliferation in human ovarian cancer cells through upregulation of AKT2. Indian J Gynecol Oncol 2019; 17(4): 85.
  13. Abbastabar M, Sarfi M, Golestani A, Khalili E. lncRNA involvement in hepatocellular carcinoma metastasis and prognosis. EXCLI J 2018; 17: 900-13.
  14. Joshi M, Rajender S. Long non-coding RNAs (lncRNAs) in spermatogenesis and male infertility. Reprod Biol Endocrinol 2020; 18(1): 103.
  15. Li L, Zhang M, Chen W, Wang R, Ye Z, Wang Y, et al. LncRNA-HOTAIR inhibition aggravates oxidative stress-induced H9c2 cells injury through suppression of MMP2 by miR-125. Acta Biochim Biophys Sin (Shanghai) 2018; 50(10): 996-1006.
  16. Mozdarani H, Ezzatizadeh V, Rahbar PR. The emerging role of the long non-coding RNA HOTAIR in breast cancer development and treatment. J Transl Med 2020; 18(1): 152.
  17. Zhang L, Liu Z, Li X, Zhang P, Wang J, Zhu D, et al. Low long non-coding RNA HOTAIR expression is associated with down-regulation of Nrf2 in the spermatozoa of patients with asthenozoospermia or oligoasthenozoospermia. Int J Clin Exp Pathol 2015; 8(11): 14198-205.
  18. Cooper TG, Noonan E, von ES, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010; 16(3): 231-45.
  19. Nateghian Z, Dashti GR, Baghazadeh S, Golshan-Iranpour F. Effects of keeping semen samples in 4-6 °C on sperm motility, viability and dna denaturation. J Isfahan Med Sch 2016; 34(401): 1181-6. [In Persian].
  20. Golshan-Iranpour f, Zamani Rarani F, Dashti GR. Effect of chromatin condensation on frozen-thawed sperm DNA integrity in normozoospermic men. Sci J Kurdistan Univ Med Sci 2019; 24(3): 34-42. [In Persian].
  21. Sefidgar Tehrani M, Amirian M, Jalali M, Attaranzadeh A, Fazel A, Ebrahimzadeh Bideskan Al. Comparison of intracytoplasmic sperm injection outcome with sperm selection techniques in oligoasthenozoospermic males: A randomized controlled trial. Iran Red Crescent Med J 2019; 21(1): E70656.
  22. O'Neill CL, Parrella A, Keating D, Cheung S, Rosenwaks Z, Palermo GD. A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment. J Assist Reprod Genet 2018; 35(10): 1911-7.
  23. Li MW, Lloyd KCK. DNA fragmentation index (DFI) as a measure of sperm quality and fertility in mice. Sci Rep 2020; 10(1): 3833.
  24. 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(1): 58-64.
  25. Muratori M, Pellegrino G, Mangone G, Azzari C, Lotti F, Tarozzi N, et al. DNA fragmentation in viable and non-viable spermatozoa discriminates fertile and subfertile subjects with similar accuracy. J Clin Med 2020; 9(5).
  26. Evgeni E, Lymberopoulos G, Gazouli M, Asimakopoulos B. Conventional semen parameters and DNA fragmentation in relation to fertility status in a Greek population. Eur J Obstet Gynecol Reprod Biol 2015; 188: 17-23.
  27. Ghasemi N, Dashti G, Amoozgar F, Vaez SA. Effect of cholesterol, iron and vitamin E on protamine deficiency and dna fragmentation of male rabbit sperm. J Isfahan Med Sch 2013; 31(259): 1769-78. [In Persian].
  28. Ajina T, Ammar O, Haouas Z, Sallem A, Ezzi L, Grissa I, et al. Assessment of human sperm DNA integrity using two cytochemical tests: Acridine orange test and toluidine blue assay. Andrologia 2017; 49(10): 1-6.
  29. Gao L, Wang X, Guo S, Xiao L, Liang C, Wang Z, et al. LncRNA HOTAIR functions as a competing endogenous RNA to upregulate SIRT1 by sponging miR-34a in diabetic cardiomyopathy. J Cell Physiol 2019; 234(4): 4944-58.
  30. Meng K, Jiao J, Zhu RR, Wang BY, Mao XB, Zhong YC, et al. The long noncoding RNA hotair regulates oxidative stress and cardiac myocyte apoptosis during ischemia-reperfusion injury. Oxid Med Cell Longev 2020; 2020: 1645249.
  31. Xu G, Zhang W, Wang Z, Chen M, Shi B. Matrine regulates H2O2-induced oxidative stress through long non-coding RNA HOTAIR/miR-106b-5p axis via AKT and STAT3 pathways. Biosci Rep 2020; 40(5): BSR20192560.
  32. Liu J, Huang GQ, Ke ZP. Silence of long intergenic noncoding RNA HOTAIR ameliorates oxidative stress and inflammation response in ox-LDL-treated human macrophages by upregulating miR-330-5p. J Cell Physiol 2019; 234(4): 5134-42.

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سابقه مقاله

  • تاریخ دریافت: 29 تیر 1400
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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