en پلی مورفیسم در ژن فعال ساز پلاسمینوژن بافتی (t-PA)، غلظت سمینال t-PA و اختلال باروری مردان: یک مطالعه مورد شاهدی Fertility & Infertility Original Article Original Article <strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">مقدمه: </span></span></strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">فعال</span></span><span dir="LTR"><span style="font-family:Arial,sans-serif;"><span style="font-size:11.0pt;">&shy;</span></span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">ساز پلاسمینوژن بافتی (</span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">) یک پروتئین است که در سیستم فیبرنولیتیک باعث کاتالیز تبدیل پلاسمینوژن به پلاسمین فعال می&shy;شود. فعالیت&nbsp; &nbsp;</span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> به وسیله مهارکننده 1 فعال&shy;ساز پلاسمینوژن کنترل می&shy;شود. </span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> نقش اساسی در اسپرماتوژنز دارد. یک پلی</span></span><span dir="LTR"><span style="font-family:Arial,sans-serif;"><span style="font-size:11.0pt;">&shy;</span></span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">مورفیسم برای ژن </span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> گزارش شده است که به صورت حضور (</span></span>^{<span style="font-size:10.0pt;">+</span>}<em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">) یا عدم حضور (</span></span><em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em>^{<span dir="LTR"><span style="font-size:10.0pt;">-</span></span>}<span style="font-family:B Mitra;"><span style="font-size:11.0pt;">) یک تکرار 300 بازی </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">می&shy;باشد.</span></span><br> <strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">هدف: </span></span></strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">مطالعه حاضر جهت بررسی ارتباط بین پلی&shy;مورفیسم </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">در ژن </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span></em><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> و ناباروری مردان طراحی شد.</span></span><br> <strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">مواد و روش &shy;ها:</span></span></strong> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">با استفاده از واکنش زنجیره&shy;ای پلی&shy;مراز بر روی </span></span><span dir="LTR"><span style="font-size:10.0pt;">DNA</span></span> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">استخراج شده از خون 79 شرکت&shy;کننده در مطالعه یک ناحیه پلی&shy;مورفیک برای درج ماده </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">در ژن </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span></em><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> تکثیر شد. به علاوه، غلظت کلی </span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">، غلظت کمپلکس مهارکننده 1 فعال&shy;ساز پلاسمینوژن به </span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> و فعالیت </span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> در پلاسمای سمینال به وسیله تکنیک الیزا اندازه&shy;گیری شد.&nbsp; </span></span><br> <strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">نتایج: </span></span></strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">میزان پلی&shy;مورفیسم&shy;های مختلف </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">ژن </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span></em> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">به صورت هوموزیگوت درج </span></span>&nbsp;<em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">(</span></span>^{<span style="font-size:10.0pt;">+/+</span>}<em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">)، هتروزیگوت </span></span>^{<span style="font-size:10.0pt;">+/-</span>}<em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> و هوموزیگوت حذف </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em>^{<span dir="LTR"><span style="font-family:Arial,sans-serif;"><span style="font-size:11.0pt;">-/-</span></span></span>}<span dir="LTR"><span style="font-family:Arial,sans-serif;"><span style="font-size:11.0pt;">) </span></span></span><em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">) در 50 فرد نابارور شرکت&shy;کننده تفاوتی با 29 فرد کنترل نداشت (به ترتیب 85/0 و</span></span> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">81/0</span></span> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">،43/0</span></span><span dir="LTR"><span style="font-size:10.0pt;">p= </span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">). از طرف دیگر، یک کاهش معنی&shy;دار در غلظت کلی </span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> در پلاسمای سمینال افراد نابارور در مقایسه با افراد کنترل مشاهده شد (0001/0 </span></span><span dir="LTR"><span style="font-size:10.0pt;">p=</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">). به هر حال، نتایج مشخص کرد که ارتباطی بین ژنوتیپ&shy;های مختلف&nbsp;</span></span><em><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span></em> <em><span dir="LTR"><span style="font-size:10.0pt;">Alu</span></span></em> <span style="font-family:B Mitra;"><span style="font-size:11.0pt;">و غلظت کلی سمینال </span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> در مردان نابارور در مقایسه با افراد کنترل وجود ندارد (63/0 </span></span><span dir="LTR"><span style="font-size:10.0pt;">p=</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">).</span></span><br> <strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">نتیجه &shy;گیری: </span></span></strong><span style="font-family:B Mitra;"><span style="font-size:11.0pt;">اطلاعات بدست آمده از مطالعه حاضر از ارتباط بین پلی&shy;مورفیسم </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">t-PA Alu</span></span></em><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> و غلظت سمینال </span></span><span dir="LTR"><span style="font-size:10.0pt;">t-PA</span></span><span style="font-family:B Mitra;"><span style="font-size:11.0pt;"> و ناباروری مردان حمایت نکرد.</span></span><span style="font-family:B Mitra;"><span style="font-size:10.0pt;"></span></span> <strong>Background:</strong> 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 <em>t-PA</em> gene, either the presence of a 300-bp <em>Alu</em>-repeat (<em>Alu</em>⁺) or its absence (<em>Alu</em>^-).<br> <strong>Objective:</strong> The current work aimed at studying the association between <em>Alu</em> polymorphism in the <em>t-PA</em> gene and male infertility.<br> <strong>Materials and Methods:</strong> Using polymerase chain reaction on genomic DNA isolated from the blood of 79 participants, a region polymorphic for <em>Alu</em> element insertion in <em>t-PA</em> 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.<br> <strong>Results:</strong> The results indicate that the percentage of infertile participants (n = 50) who were homozygous for <em>t-PA</em> <em>Alu</em> insertion (<em>Alu^+/+</em>), heterozygous <em>Alu^+/-</em> or homozygous for <em>t-PA</em> <em>Alu</em> deletion (<em>Alu^-/-</em>) 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 <em>t-PA</em> <em>Alu</em> <a name="OLE_LINK1"></a>different genotypes and the total t-PA seminal concentration in the infertile group when compared to the control group (p = 0.63).<br> <strong>Conclusion:</strong> Data obtained from the current study does not support an association between <em>t-PA Alu</em> polymorphism and t-PA seminal concentration or male infertility.<br> &nbsp; ماده Alu, ناباروری مردان, مایع منی, اسپرماتوژنز, t-PA. Alu element, Male infertility, Semen, Spermatogenesis, t-PA. 571 578 http://ijrm.ir/browse.php?a_code=A-10-1037-1&slc_lang=en&sid=1 Lubna Hamid Tahtamouni lubnatahtamuni@hu.edu.jo 0000-0001-8024-1944 Yes Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan. Department of Biochemistry and Molecular Biology, College of Natural Sciences, Colorado State University, Fort Collins, Colorado, USA. Mahmoud Nael Hamdan m.terawi@yahoo.com 0000-0001-9939-9493 No Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan. Zainab Ali Al-Mazaydeh zainab_almazaydeh@hotmail.com 0000-0003-0074-2015 No Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan. Randa Mahmoud Bawadi bawadiranda@hotmail.com 0000-0001-5011-1532 No Department of Physiology and Biochemistry, School of Medicine, the University of Jordan, Amman, Jordan. Majdoleen Sobhi Rammaha majdoleenrammaha@yahoo.com 0000-0003-3029-4196 No Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan. Ahmad Mohammad Zghoul alzghoul_99@outlook.com 0000-0003-1084-6969 No Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan. Mamoun Ahmad Ahram dr.ahram@gmail.com 0000-0003-4457-3604 No Department of Physiology and Biochemistry, School of Medicine, the University of Jordan, Amman, Jordan. Salem Yasin salemmaloul@yahoo.com 0000-0002-0251-1192 No Department of Biology and Biotechnology, Faculty of Science, the Hashemite University, Zarqa, Jordan.