en سکرتوم‌های سلول‌های بنیادی مزانشیمی غشای آمنیوتیک انسان، بهبودی و عملکرد بیضه را از طریق تعدیل مسیر سیگنالینگ SIRT1/NRF2/TNF-α در پیچ خوردگی بیضه موش افزایش می‌دهد: یک مطالعه تجربی Reproductive Anatomy Original Article Original Article <div style="text-align: justify;"><span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مقدمه: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">آسیب ایسکمی/رپرفیوژن بیضه (</span></span><span dir="LTR" style="font-size:10.0pt">I/R</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) که متعاقب پیچ&shy;خوردگی بیضه ایجاد می&shy;شود، می&shy;تواند منجر به ناباروری مردان شود.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">هدف: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مطالعه حاضر با هدف بررسی اثر سکرتوم&shy;های سلول&shy;های بنیادی مزانشیمی مشتق از غشای آمنیوتیک انسان (</span></span><span dir="LTR" style="font-size:10.0pt">hAMSCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) بر تورشن/دتورشن بیضه در موش سوری انجام شد.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مواد و روش&shy; ها:</span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> کل آزمایشات در گروه آناتومی دانشگاه علوم پزشکی تهران، تهران، ایران در تاریخ اسفند ماه 1401 تا دی ماه 1402 انجام شد. 40</span></span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">سر موش نر (5 تا 7 هفته، 25 تا 30 گرم) به طور تصادفی به چهار گروه زیر تقسیم شدند: 1) گروه شم: موش‌ها فقط جراحی ساختگی داشتند و مداخله&shy;ی دیگری دریافت نکردند. 2) گروه تورشن/دتورشن، 3) گروه کنترل منفی: تورشن/دتورشن </span></span><span lang="FA" style="font-size:10.0pt">+</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> تزریق داخل بیضه</span></span> <span dir="LTR" style="font-size:10.0pt">DMEM/F-12</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">و 4) گروه تورشن/دتورشن </span></span><span lang="FA" style="font-size:10.0pt">+</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> تزریق داخل بیضه فاکتورهای ترشح&shy;کننده</span></span> <span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">.</span></span><span dir="LTR" style="font-size:10.0pt">hAMSCs</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">سطوح سرمی تستوسترون، رنگ&shy;آمیزی </span></span><span dir="LTR" style="font-size:10.0pt">H&E</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و پارامترهای کیفیت اسپرم برای ارزیابی اثرات درمانی فاکتورهای ترشح شده </span></span><span dir="LTR" style="font-size:10.0pt">hAMSCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> بر ساختار و عملکرد بیضه استفاده شد. استرس اکسیداتیو بافتی با تعیین مالون&shy;دی&shy;آلدئید، سوپراکسید دیسموتاز، کاتالاز و گلوتاتین پراکسیداز 1 اندازه‌گیری شد. بیان </span></span><span dir="LTR" style="font-size:10.0pt">mRNA</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">Nrf2</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، </span></span><i><span dir="LTR" style="font-size:10.0pt">Keap1</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، </span></span><i><span dir="LTR" style="font-size:10.0pt">Sirt1</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، </span></span><i><span dir="LTR" style="font-size:10.0pt">TNF-&alpha;</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><i><span dir="LTR" style="font-size:10.0pt">P53</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در بیضه از طریق واکنش زنجیره&shy;ای پلیمراز ارزیابی شدند.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتایج: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتایج نشان داد که عوامل ترشح&shy;شده از </span></span><span dir="LTR" style="font-size:10.0pt">hAMSC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> با کاهش استرس اکسیداتیو، پاسخ التهابی و آپوپتوز از طریق تعدیل مسیر سیگنالینگ </span></span><span dir="LTR" style="font-size:10.0pt">Sirt1/Nrf2/TNF-&alpha;</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، آسیب تورشن-دتورشن بیضه را کاهش می‌دهند.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتیجه&shy; گیری: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">فاکتورهای ترشح شده از </span></span><span dir="LTR" style="font-size:10.0pt">hAMSCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> باعث افزایش توان آنتی&shy;اکسیدانی، ضد التهابی و ضد آپوپتوز شد که در نتیجه باعث افزایش سطح تستوسترون، اسپرم&shy;زایی و پارامترهای کیفیت اسپرم گردید.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br> &nbsp;</div> <div style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><b><span style="font-size:12.0pt">Background:</span></b><span style="font-size:12.0pt"> Testicular ischemia/reperfusion injury, a significant result of testicular torsion, can lead to the risk of male infertility. </span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><b><span style="font-size:12.0pt">Objective:</span></b><span style="font-size:12.0pt"> The current study aimed to evaluate the effect of </span><span style="font-size:12.0pt">human amniotic membrane-derived mesenchymal stem cells (hAMSCs) secretome</span><span style="font-size:12.0pt"> on testicular torsion/detorsion (T/D) in </span><span style="font-size:12.0pt">mice.</span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><b><span style="font-size:12.0pt">Materials and Methods:</span></b><span style="font-size:12.0pt"> All the experiments were performed in the Anatomy Department of Tehran University of Medical Sciences, Tehran, Iran, during the period of March 2023 to December 2023. </span><span style="font-size:12.0pt">40 male NMRI mice</span><span style="font-size:12.0pt"> (5-7 wk, 25-30 gr) w</span><span style="font-size:12.0pt">ere randomized into: 1) the sham group: </span><span style="font-size:12.0pt">mice</span><span style="font-size:12.0pt"> received sham operations with no other interventions, 2) T/D group, 3) negative control group; </span><span style="font-size:12.0pt">torsion detorsion + intratesticular injection of</span> <span style="font-size:12.0pt">Dulbecco&#39;s Modified Eagle Medium/Nutrient Mixture F-12</span><span style="font-size:12.0pt">, and 4) the T/D group + </span><span style="font-size:12.0pt">hAMSCs secreted factors</span><span style="font-size:12.0pt">. Serum testosterone levels, hematoxylin and eosin staining, and sperm quality parameters were used to evaluate the therapeutic effects of</span><span style="font-size:12.0pt"> hAMSCs secreted factors on the testicular structure and function. Tissue oxidative stress was measured by determining malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase-1. Nuclear factor erythroid 2-related factor 2, Kelch-like ECH-associated protein 1, NAD-dependent deacetylase sirtuin-1, tumor necrosis factor-alpha and tumor protein P53 <span class="A6" style="color:black">mRNA </span>expressions were assessed in testis via real-time polymerase chain reaction.</span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><b><span style="font-size:12.0pt">Results<i>:</i></span></b><span style="font-size:12.0pt"> The results showed that hAMSCs secreted factors alleviated testicular T/D injury by attenuating oxidative stress, inflammatory response, and apoptosis via modulating the sirtuin-1/ nuclear factor erythroid 2-related factor 2/tumor necrosis factor-alpha signaling pathway.</span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="unicode-bidi:embed"><b><span style="font-size:12.0pt">Conclusion:</span></b><span style="font-size:12.0pt"> hAMSCs secreted factors increased antioxidative, anti-inflammatory, and antiapoptotic properties which consequently increased testosterone levels, spermatogenesis, and sperm quality parameters.</span></span></span></span></span></div> آسیب خونرسانی مجدد, سلول‌های بنیادی مزانشیمی, سکرتوم, استرس اکسیداتیو. Reperfusion injury, Mesenchymal stem cells, Secretome, Oxidative stress. 821 836 http://ijrm.ir/browse.php?a_code=A-10-2668-1&slc_lang=en&sid=1 Roghayeh Esfehani r.esfahani999@gmail.com 0009-0007-4280-3177 No Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Farnaz Khadivi farnazkhadivi031@gmail.com 0000-0003-1712-4870 No Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. Jamal Valipour jamalvalipour1371@yahoo.com 0000-0003-0481-6499 No Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Maryam Shabani maryamshabani1@gmail.com 0000-0002-5813-0655 No Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Mahya Ramesh mahyaramesh1@gmail.com 0000-0003-3767-0262 No Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Parinaz Javanbakht parinaz.javannnbakht@gmail.com 0000-0002-6680-4613 No Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Davood Zarini zeuseta@yahoo.com 0000-0002-9264-7738 No Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Sina Mojaverrostami smojaver@sina.tums.ac.ir 0000-0001-5479-1168 Yes Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Masih Hoseini masihosseini11@gmail.com 0000-0003-2785-5247 No Department of Anatomy, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.