بررسی ارتباط miR34c ، miR15b ،کیفیت پارامترهای اسپرمی و میزان شکست DNA اسپرم در افراد نابارور اولیگو آستنو تراتوزو اسپرمی
محورهای موضوعی :
مجله پلاسما و نشانگرهای زیستی
راحیل جنتی فر
1
,
فاطمه دهقانی
2
,
فاطمه توحیدی
3
1 - گروه پژوهشی بیولوژی تولید مثل، واحد تحقیقات جهاددانشگاهی، قم،ایران
2 - گروه ژنتیک، دانشکده علوم پایه، موسسه آموزش عالی آل طه، تهران، ایران
3 - گروه ژنتیک، دانشکده علوم پایه، موسسه آموزش عالی آل طه، تهران، ایران
تاریخ دریافت : 1402/05/31
تاریخ پذیرش : 1402/06/25
تاریخ انتشار : 1402/08/01
کلید واژه:
miR15b,
miR34c,
اسپرم,
اولیگو آستنو تراتوزواسپرمی,
چکیده مقاله :
مقدمه: : MiRNA ها نقش مهمی فرایندهای مختلف پاتوفیزیولوژیک در سلولها و کنترل فرایند آپوپتوز در اسپرم دارند. هدف این پژوهش بررسی ارتباط بیان miR34cو miR15b های ، کیفیت پارامترهای اسپرمی و میزان شکست DNA اسپرم در افراد نابارور اولیگو استنو تراتوزواسپرمی می باشد.روش کار: این مطالعه بر روی 25 بیمار دارای اولیگو آستنو تراتوزواسپرمی که به مرکز درمان ناباروری جهاد دانشگاهی قم مراجعه کرده بودند انجام شد. 25 نفر از افراد بارور هم به عنوان گروه کنترل انتخاب شده اند. بعد از جمع آوری نمونه های اسپرمی ، پارامترهای اسپرمی بر اساس سازمان بهداشت جهانی ( WHO2010) آنالیز شدند. میزان شکست DNA اسپرم با استفاده از تکنیک SCD)) بررسی شد. میزان بیان miR34cو miR15b با استفاده از تکنیک Rael-time PCR اندازه گیری شد.نتایج: طبق نتایج به دست آمده پارامترهای اسپرمی از جمله غلظت ، تحرک و مورفولوژی اسپرم در افراد نابارور اولیگو آستنو تراتوزواسپرمی نسبت به افراد بارور کاهش معنی داری را نشان می دهد (P<0.05) و میزان شکست DNA اسپرم در افراد اولیگو آستنو تراتوزواسپرمی افزایش معنی داری داشت(P<0.05). آزمون همبستگی مشخص کرد که بین متغیرهای اسپرم شامل غلظت، تحرک ، مورفولوژی نرمال، میزان شکست DNA اسپرم و میزان بیان miR34c و miR15b همبستگی معنی داری وجود دارد .نتیجه گیری: یافته های ما نشان داد که بین بیان miR34c ، miR15b ، پارامترهای اسپرمی و سلامت DNA اسپرم ارتباط معنی داری وجود دارد. در واقع این نتایج می تواند بینش جدیدی برای تشخیص ناباروری مردان در سطح مولکولی ارائه کند.
چکیده انگلیسی:
Introduction: MiRNAs play an important role in various pathophysiological processes in cells and controlling the process of apoptosis in sperm. The aim of this study is to investigate the relationship between the expression of miR34c and miR15b, the quality of sperm parameters and the rate of sperm DNA breakage in oligoasthenoteratozoospermia infertile individuals.Methods: This study was conducted on 25 patients with oligoasthenoteratozoospermia who had referred to Jihad University Infertility Treatment Center in Qom. 25 fertile people have been selected as the control group. After collecting sperm samples, sperm parameters were analyzed according to the World Health Organization (WHO 2010). The amount of sperm DNA breakage was checked using the SCD technique. The expression levels of miR34c and miR15b were measured using the Rael-time PCR technique.Results: According to the obtained results, sperm parameters such as concentration, motility and morphology of sperm in infertile oligoasthenoteratozoospermia individuals show a significant decrease compared to fertile individuals (P<0.05) and the rate of sperm DNA breakage in oligoasthenoteratozoospermia individuals increases. It was significant (P<0.05). Correlation test revealed that there is a significant correlation between sperm variables including concentration, motility, normal morphology, sperm DNA breakage rate and the expression level of miR34c and miR15b.Conclusion: Our findings showed that there is a significant relationship between the expression of miR34c, miR15b, sperm parameters and sperm DNA health. In fact, these results can provide new insights for the diagnosis of male infertility at the molecular level.
منابع و مأخذ:
Organization WH. Improving the quality and use of birth, death and cause-of-death information: guidance for a standards-based review of country practices. 2010.
2. Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HG, Behre HM, et al. World Health Organization reference values for human semen characteristics. Human reproduction update. 2010;16(3):231-45.
3. Burgos C, Cikutovic R, Alarcon M. MicroRNA expression in male infertility. Reproduction, Fertility and Development. 2022.
4. Curry E, Safranski TJ, Pratt SL. Differential expression of porcine sperm microRNAs and their association with sperm morphology and motility. Theriogenology. 2011;76(8):1532-9.
5. Amanai M, Brahmajosyula M, Perry AC. A restricted role for sperm-borne microRNAs in mammalian fertilization. Biology of reproduction. 2006;75(6):877-84.
6. Agostini M, Knight RA. miR-34: from bench to bedside. Oncotarget. 2014;5(4):872.
7. Bouhallier F, Allioli N, Lavial F, Chalmel F, Perrard M-H, Durand P, et al. Role of miR-34c microRNA in the late steps of spermatogenesis. Rna. 2010;16(4):720-31.
8. Abu-Halima M, Hammadeh M, Backes C, Fischer U, Leidinger P, Lubbad AM, et al. Panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility. Fertility and sterility. 2014;102(4):989-97. e1.
9. Yue J, Tigyi G. Conservation of miR-15a/16-1 and miR-15b/16-2 clusters. Mammalian Genome. 2010;21:88-94.
10. Ramaiah MJ. Functions and epigenetic aspects of miR-15/16: Possible future cancer therapeutics. Gene Reports. 2018 Sep 1;12:149-64.
11. Organization WH. World health statistics 2010: World Health Organization; 2010.
12. Belleannée C, Calvo E, Thimon V, Cyr DG, Légaré C, Garneau L, et al. Role of microRNAs in controlling gene expression in different segments of the human epididymis. PloS one. 2012;7(4):e34996.
Björkgren I, Gylling H, Turunen H, Huhtaniemi I, Strauss L, Poutanen M, et al. Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane. The FASEB Journal. 2015;29(2):433-42.
Tong MH, Mitchell DA, McGowan SD, Evanoff R, Griswold MD. Two miRNA clusters, Mir-17-92 (Mirc1) and Mir-106b-25 (Mirc3), are involved in the regulation of spermatogonial differentiation in mice. Biology of reproduction. 2012 Mar 1;86(3):72-1.15. Comazzetto S, Di Giacomo M, Rasmussen KD, Much C, Azzi C, Perlas E, et al. Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci. PLoS genetics. 2014;10(10):e1004597.
Zhang S, Chen L, Jung EJ, Calin GA. Targeting microRNAs with small molecules: from dream to reality. Clinical Pharmacology & Therapeutics. 2010;87(6):754-8.
Tomic M, Bolha L, Pizem J, Ban-Frangez H, Vrtacnik-Bokal E, Stimpfel M. Association between Sperm Morphology and Altered Sperm microRNA Expression. Biology. 2022;11(11):1671.
Taheri H, Hosseini S, Salehi M.The relationship between Sperm DNA fragmentation and differential expression of human sperm pro-apoptotic miR-15a/16 and anti-apoptotic BCL-2 gene. The Iranian Journal of Obstetrics, Gynecology and Infertility.2019;22(10);42-48.
Buñay J, Larriba E, Patiño-Garcia D, Urriola-Muñoz P, Moreno RD, Del Mazo J. Combined proteomic and miRNome analyses of mouse testis exposed to an endocrine disruptors chemicals mixture reveals altered toxicological pathways involved in male infertility. MHR: Basic science of reproductive medicine. 2019;25(3):156-69.
Shaoqin G, Zhenghui Z, Xueqian Z, Yuan H. Epigenetic modifications in human spermatozoon and its potential role in embryonic development. Yi chuan= Hereditas. 2014;36(5):439-46.
Rajender S, Avery K, Agarwal A. Epigenetics, spermatogenesis and male infertility. Mutation Research/Reviews in Mutation Research. 2011;727(3):62-71.
22. Miller D, Brinkworth M, Iles D. Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics. Reproduction. 2010;139(2):287-301.
Pradeepa M, Manjunatha S, Sathish V, Agrawal S, Rao M. Involvement of importin-4 in the transport of transition protein 2 into the spermatid nucleus. Molecular and cellular biology. 2008;28(13):4331-41.
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Organization WH. Improving the quality and use of birth, death and cause-of-death information: guidance for a standards-based review of country practices. 2010.
2. Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HG, Behre HM, et al. World Health Organization reference values for human semen characteristics. Human reproduction update. 2010;16(3):231-45.
3. Burgos C, Cikutovic R, Alarcon M. MicroRNA expression in male infertility. Reproduction, Fertility and Development. 2022.
4. Curry E, Safranski TJ, Pratt SL. Differential expression of porcine sperm microRNAs and their association with sperm morphology and motility. Theriogenology. 2011;76(8):1532-9.
5. Amanai M, Brahmajosyula M, Perry AC. A restricted role for sperm-borne microRNAs in mammalian fertilization. Biology of reproduction. 2006;75(6):877-84.
6. Agostini M, Knight RA. miR-34: from bench to bedside. Oncotarget. 2014;5(4):872.
7. Bouhallier F, Allioli N, Lavial F, Chalmel F, Perrard M-H, Durand P, et al. Role of miR-34c microRNA in the late steps of spermatogenesis. Rna. 2010;16(4):720-31.
8. Abu-Halima M, Hammadeh M, Backes C, Fischer U, Leidinger P, Lubbad AM, et al. Panel of five microRNAs as potential biomarkers for the diagnosis and assessment of male infertility. Fertility and sterility. 2014;102(4):989-97. e1.
9. Yue J, Tigyi G. Conservation of miR-15a/16-1 and miR-15b/16-2 clusters. Mammalian Genome. 2010;21:88-94.
10. Ramaiah MJ. Functions and epigenetic aspects of miR-15/16: Possible future cancer therapeutics. Gene Reports. 2018 Sep 1;12:149-64.
11. Organization WH. World health statistics 2010: World Health Organization; 2010.
12. Belleannée C, Calvo E, Thimon V, Cyr DG, Légaré C, Garneau L, et al. Role of microRNAs in controlling gene expression in different segments of the human epididymis. PloS one. 2012;7(4):e34996.
Björkgren I, Gylling H, Turunen H, Huhtaniemi I, Strauss L, Poutanen M, et al. Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane. The FASEB Journal. 2015;29(2):433-42.
Tong MH, Mitchell DA, McGowan SD, Evanoff R, Griswold MD. Two miRNA clusters, Mir-17-92 (Mirc1) and Mir-106b-25 (Mirc3), are involved in the regulation of spermatogonial differentiation in mice. Biology of reproduction. 2012 Mar 1;86(3):72-1.15. Comazzetto S, Di Giacomo M, Rasmussen KD, Much C, Azzi C, Perlas E, et al. Oligoasthenoteratozoospermia and infertility in mice deficient for miR-34b/c and miR-449 loci. PLoS genetics. 2014;10(10):e1004597.
Zhang S, Chen L, Jung EJ, Calin GA. Targeting microRNAs with small molecules: from dream to reality. Clinical Pharmacology & Therapeutics. 2010;87(6):754-8.
Tomic M, Bolha L, Pizem J, Ban-Frangez H, Vrtacnik-Bokal E, Stimpfel M. Association between Sperm Morphology and Altered Sperm microRNA Expression. Biology. 2022;11(11):1671.
Taheri H, Hosseini S, Salehi M.The relationship between Sperm DNA fragmentation and differential expression of human sperm pro-apoptotic miR-15a/16 and anti-apoptotic BCL-2 gene. The Iranian Journal of Obstetrics, Gynecology and Infertility.2019;22(10);42-48.
Buñay J, Larriba E, Patiño-Garcia D, Urriola-Muñoz P, Moreno RD, Del Mazo J. Combined proteomic and miRNome analyses of mouse testis exposed to an endocrine disruptors chemicals mixture reveals altered toxicological pathways involved in male infertility. MHR: Basic science of reproductive medicine. 2019;25(3):156-69.
Shaoqin G, Zhenghui Z, Xueqian Z, Yuan H. Epigenetic modifications in human spermatozoon and its potential role in embryonic development. Yi chuan= Hereditas. 2014;36(5):439-46.
Rajender S, Avery K, Agarwal A. Epigenetics, spermatogenesis and male infertility. Mutation Research/Reviews in Mutation Research. 2011;727(3):62-71.
22. Miller D, Brinkworth M, Iles D. Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics. Reproduction. 2010;139(2):287-301.
Pradeepa M, Manjunatha S, Sathish V, Agrawal S, Rao M. Involvement of importin-4 in the transport of transition protein 2 into the spermatid nucleus. Molecular and cellular biology. 2008;28(13):4331-41.
