en نقش احتمالی تنظیمی miR-4463 و ژن هدف آن CYP19A1 بر پاسخ تخمدانی در بیماران با کاهش ذخیره تخمدانی: یک مطالعه مورد-شاهدی Reproductive Genetics 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:">کاهش ذخیره تخمدان (</span></span><span dir="LTR" style="font-size:10.0pt">DOR</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) وضعیتی است که با کاهش پتانسیل تولید&shy;مثلی تخمدان، باروری را تحت تأثیر قرار می&shy;دهد. این وضعیت ممکن است به دلیل بیماری، آسیب یا افزایش سن رخ دهد. تغییر پروفایل بیان سلول&shy;های کومولوس (</span></span><span dir="LTR" style="font-size:10.0pt">CCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) می&shy;تواند بر کیفیت و کمیت تخمک&shy;ها در تخمدان تأثیر منفی بگذارد. بنابراین، ارزیابی ذخیره تخمدان و شخصی&shy;سازی برنامه&shy;های دارویی برای افزایش میزان موفقیت روش&shy;های کمک باروری (</span></span><span dir="LTR" style="font-size:10.0pt">ART</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) ضروری است. مطالعات اخیر نشان می&shy;دهد که </span></span><span dir="LTR" style="font-size:10.0pt">miRNA</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های در گردش نقش مهمی در عملکرد تخمدان دارند و تغییرات بیان سرمی آنها می</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">تواند نشانگرهای زیستی ارزشمندی برای&nbsp;&nbsp; &nbsp;پیش</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">بینی عملکرد تخمدان باشد.</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:">بررسی سطح بیان </span></span><span dir="LTR" style="font-size:10.0pt">miRNA-4463</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در گردش و ژن هدف آن </span></span><i><span dir="LTR" style="font-size:10.0pt">CYP19A1</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در سلول&shy;های کومولوس زنان مبتلا به </span></span><span dir="LTR" style="font-size:10.0pt">DOR</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> می&shy;باشد.</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:">مواد و روش &shy;ها: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در این مطالعه مورد-شاهدی، 20 زن </span></span><span dir="LTR" style="font-size:10.0pt">DOR</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و 20 زن با پاسخ تخمدان طبیعی 34-20 ساله که به پژوهشکده علوم تولید</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مثل یزد مراجعه کرده بودند، مورد بررسی قرار گرفتند. برای تجزیه و تحلیل سطح بیان </span></span><span dir="LTR" style="font-size:10.0pt">miR-4463</span><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">CYP19A1</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در سلول‌های کومولوس آن‌ها،</span></span><span dir="LTR" style="font-size:10.0pt">PCR </span>&nbsp;<span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">کمی انجام شد.</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:">سطح بیان </span></span><span dir="LTR" style="font-size:10.0pt">miRNA-4463</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و ژن هدف کاندید آن </span></span><i><span dir="LTR" style="font-size:10.0pt">CYP19A1</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> بین گروه&shy;ها مقایسه شد. مطالعه ما نشان می&shy;دهد که یک رابطه معکوس بین سطوح بیان </span></span><span dir="LTR" style="font-size:10.0pt">miR-4463</span><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">CYP19A1</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> وجود دارد. بطوریکه افزایش در بیان </span></span><span dir="LTR" style="font-size:10.0pt">miR-4463</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> بطور معنی&shy;داری در زنان مبتلا به کاهش ذخیره تخمدان نسبت به گروه کنترل مشاهده شد (0019/0 </span></span><span lang="FA" style="font-size:10.0pt">= </span><span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">). در حالیکه بیان ژن هدف آن، کاهش معنی&shy;داری را در این زنان نشان داد (001/0 </span></span><span lang="FA" style="font-size:10.0pt">= </span><span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">).</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:">مطالعه حاضر نشان می</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">دهد که مسیرهای </span></span><span dir="LTR" style="font-size:10.0pt">miR-4463</span><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">CYP19A1</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> می&shy;توانند عملکرد تخمدان را تنظیم کنند. بنابراین، بررسی این </span></span><span dir="LTR" style="font-size:10.0pt">miRNA</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> می‌تواند پارامتر امیدوار کننده‌ای برای پیش‌بینی ذخیره تخمدان و پاسخ آن‌ها به پروتکل‌های تحریکی باشد.</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></div> <div style="text-align: justify;"><span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="text-autospace:none"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Background</span></span></b><b><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">:</span></span></b><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> Diminished ovarian reserve (DOR) is a condition that affects fertility by reducing the reproductive potential of the ovary. The altered expression profile of cumulus cells (CCs) can negatively affect the quality and quantity of oocytes in the ovaries. Recent studies suggest that circulating miRNAs play a significant role in the ovary function, and their serum expression changes can be valuable biomarkers for predicting ovarian function. </span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="text-autospace:none"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Objective</span></span></b><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> Investigating the expression levels of circulating miRNA-4463 and its target cytochrome P450 19A1 gene (<i>CYP19A1</i>) in DOR-CCs in order to find a molecular pathway involved in </span></span><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">DOR.</span></span><span dir="RTL" lang="AR-SA" style="font-size:12.0pt"><span style="font-family:"Times New Roman","serif""></span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="text-autospace:none"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Materials and Methods</span></span></b><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> In this case-control study, a total of </span></span><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">20 </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">DOR</span></span><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">-women</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> and 20 women with normal ovarian reservation aged between</span></span><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> 20-34 yr</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> referred to Yazd Reproductive Science Institute, Yazd, Iran were included in the study. Serum and </span></span><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">CCs were collected, and </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">real time-polymerase chain reaction was performed to investigate the expression level of miR-4463<i>, </i>and its target gene </span></span><i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">CYP19A1</span></span></i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">. </span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="text-autospace:none"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Results</span></span></b><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> Our results showed an inverse relationship between miR-4463 and </span></span><i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">CYP19A1</span></span></i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> expression levels. Therefore, the increase in the expression of miR-4463 was significantly evident in </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">DOR</span></span><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">-women</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> compared to the control group </span></span><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">(</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">p = 0.0019)</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">, while the expression of its target gene, </span></span><i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">CYP19A1,</span></span></i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> has significantly decreased in these women </span></span><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">(</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">p = 0.001)</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">. </span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="text-autospace:none"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Conclusion:</span></span></b> <span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">The present study suggests that miR-4463 and </span></span><i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">CYP19A1</span></span></i> <span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">pathways could be regulate ovary function. Therefore, examination of this miRNA could be a promising parameter for predicting ovarian reserve and their response to stimulation protocols.</span></span></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span sans-serif="" style="font-family:Calibri,"><span lang="EN" style="font-size:8.0pt"><span style="font-family:"Times New Roman","serif""></span></span></span></span></span></div> پاسخ تخمدانی, miR-4463 ,CYP19A, کاهش ذخیره تخمدان (DOR), سلول‌های کومولوس (CCs). Ovarian response, CYP19A, miR-4463, Diminished ovarian reserve (DOR), Cumulus cells (CCs). 639 650 http://ijrm.ir/browse.php?a_code=A-10-1088-4&slc_lang=en&sid=1 Azam Yazdanian azamyazdanian2@gmail.com 0009-0001-5343-3761 No Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Marzieh Lotfi marzeih.lotfi@gmail.com 0000-0001-7323-6717 No Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Fateme Montazeri f_montazeri@outlook.com 0000-0002-1984-951x Yes Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Saeideh Dashti saeideh_dashti@yahoo.com 0000-0001-7089-0772 No Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Mohammad Hasan Sheikhha Sheikhha@yahoo.com 0000-0002-3734-8970 No Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.