International Journal of Reproductive BioMedicine
International Journal of Reproductive BioMedicine
IJRM
Medical Sciences
http://ijrm.ir
1
admin
2476-4108
2476-3772
10.29252/ijrm
en
jalali
1403
3
1
gregorian
2024
6
1
22
6
online
1
fulltext
en
نقش تنظیمی پروتئین Smad2/3 و بیان ژن SMURF2 در سلولهای گرانولوزای تخمکهای بالغ و نابالغ بیماران سندروم تخمدان پلیکیستیک: یک مطالعه مورد-شاهدی
The regulatory roles of Smad2/3 protein and SMURF2 gene expression in granulosa cells of germinal vesicle and metaphase II oocytes in polycystic ovarian syndrome: A case-control study
Cellular and Molecular Biology of Reproduction
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:">اختلال در عملکرد سلولهای گرانولوزا (</span></span><span dir="LTR" style="font-size:10.0pt">GCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) و بدنبال آن عدم بلوغ تخمک در زنان سندرم تخمدان پلی</span></span><span lang="FA" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">کیستیک (</span></span><span dir="LTR" style="font-size:10.0pt">PCOS</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)، گزارش شده است. حتی با تحریک تخمدان، تعداد زیادی از تخمک­ها در این بیماران هنوز در مرحله وزیکول ژرمینال (</span></span><span dir="LTR" style="font-size:10.0pt">GV</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) هستند.</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:">در این مطالعه، میزان پروتئین</span></span><span lang="FA" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های </span></span><span dir="LTR" style="font-size:10.0pt">Smad2/3</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، </span></span><span dir="LTR" style="font-size:10.0pt">Smad2/3</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> فسفریله (</span></span><span dir="LTR" style="font-size:10.0pt">P-Smad2/3</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) و بیان ژنهای </span></span><i><span dir="LTR" style="font-size:10.0pt">SARA</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">SMAD4</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">SMURF2</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در سلولهای گرانولوزا (</span></span><span dir="LTR" style="font-size:10.0pt">GCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) تخمک</span></span><span lang="FA" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های بالغ </span></span><span dir="LTR" style="font-size:10.0pt">MII</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و نابالغ </span></span><span dir="LTR" style="font-size:10.0pt">GV</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در بیماران </span></span><span dir="LTR" style="font-size:10.0pt">PCOS</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> بررسی 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 روش­ها: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">سلولهای گرانولوزا (</span></span><span dir="LTR" style="font-size:10.0pt">GCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) تخمکهای </span></span><span dir="LTR" style="font-size:10.0pt">MII</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><span dir="LTR" style="font-size:10.0pt">GV</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> از 38 بیمار </span></span><span dir="LTR" style="font-size:10.0pt">PCOS</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> جدا و میزان بیان </span></span><i><span dir="LTR" style="font-size:10.0pt">SARA</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">SMURF2</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">SMAD4</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> با استفاده از </span></span><span dir="LTR" style="font-size:10.0pt">RT-qPCR</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> تعیین شد. همچنین بیان پروتئین</span></span><span dir="LTR" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های </span></span><span dir="LTR" style="font-size:10.0pt">Smad2/3</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><span dir="LTR" style="font-size:10.0pt">P-smad2/3</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">با استفاده از وسترن­بلات 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:">میزان بیان </span></span><i><span dir="LTR" style="font-size:10.0pt">SMURF2</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در </span></span><span dir="LTR" style="font-size:10.0pt">GC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های تخمک</span></span><span lang="FA" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های نابالغ در مقایسه با </span></span><span dir="LTR" style="font-size:10.0pt">GC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های تخمک</span></span><span lang="FA" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های بالغ به طور معنیداری بالاتر بود (001/0 </span></span><span dir="LTR" 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 عین حال تفاوت معنیداری در سطوح بیان </span></span><i><span dir="LTR" style="font-size:10.0pt">SARA</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">SMAD4</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در </span></span><span dir="LTR" style="font-size:10.0pt">GC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های سلول</span></span><span lang="FA" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های نابالغ وجود نداشت. همچنین در </span></span><span dir="LTR" style="font-size:10.0pt">GC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های تخمک</span></span><span dir="LTR" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های </span></span><span dir="LTR" style="font-size:10.0pt">GV</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در مقایسه با </span></span><span dir="LTR" style="font-size:10.0pt">GC</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های تخمک</span></span><span lang="FA" style="font-size:11.0pt"><span cambria="" style="font-family:">­</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های </span></span><span dir="LTR" style="font-size:10.0pt">MII</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، سطح پایینتری از </span></span><span dir="LTR" style="font-size:10.0pt">P-Smad2/3</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مشاهده شد (001/0 </span></span><span dir="LTR" 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:">نتیجه­گیری: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">به نظر میرسد </span></span><span dir="LTR" style="font-size:10.0pt">P-Smad2/3</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در رشد تخمکها نقش داشته و کاهش این پروتئین با نقص در بلوغ تخمکهای </span></span><span dir="LTR" style="font-size:10.0pt">GV</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> همراه بوده، از طرف دیگر، بیان بالای ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">SMURF2</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> نیز بر روند رشد </span></span><span dir="LTR" style="font-size:10.0pt">GCs</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> وکاهش بلوغ تخمک نابالغ </span></span><span dir="LTR" style="font-size:10.0pt">GV</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> تأثیرگذار است.</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:12pt"><span style="line-height:normal"><span new="" roman="" style="font-family:" times=""><b>Background</b><b>:</b> The impaired functions of granulosa cells (GCs) in the delayed development and immaturity of oocytes have been reported in polycystic ovary syndrome (PCOs). Even with ovarian stimulation, a large number of oocytes in these patients are still in the stage germinal vesicle (GV).</span></span></span><br>
<span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" style="font-family:" times=""><b>Objective</b><b>:</b> The levels of Smad2/3, phosphorylated Smad2/3 (P-Smad2/3), the expression of <i>SARA</i>, <i>Smad4</i>, and <i>SMURF2 </i>genes in the GCs surrounding metaphase II (MII) or GV oocytes in PCOs women were investigated.</span></span></span><br>
<span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" style="font-family:" times=""><b>Materials and Methods</b><b>:</b> GCs of MII and GV oocytes were isolated from 38 women with PCOs and the expression levels of <i>SARA,</i><i> Smad4</i><i>,</i> and <i>SMURF2 </i>in surrounding GCs of MII and GV oocytes were determined using <span style="background:white"><span style="color:black">reverse-transcription </span></span>polymerase chain reaction<i>.</i> Also, Smad2/3 and P-Smad2/3 proteins were determined using western blotting.</span></span></span><br>
<span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" style="font-family:" times=""><b>Results:</b> The expression level of <i>SMURF2</i> was significantly higher in GCs surrounding GV oocytes compared with that of GCs encompassing MII oocytes (p < 0.001). At the same time, no significant differences were observed in <i>SARA</i> and <i>Smad4</i> expression levels in GCs surrounding GV and MII oocytes. A lower level of P-Smad2/3 was also found in GCs GV oocytes compared with GCs of MII oocytes (p < 0.001).</span></span></span><br>
<span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" style="font-family:" times=""><b>Conclusion</b><b>:</b> It seems that P-Smad2/3 plays a role in oocyte development, and the downregulation of this protein is associated with a defect in the maturation of GV oocytes. On the other hand, the upregulation of the <i>SMURF2</i> gene also affects the growth process of GCs and the maturation of GV oocytes. </span></span></span></div>
تخمدان پلی کیستیک, تخمک, سلول های گرانولوزا.
Polycystic ovary, Oocytes, Granulosa cell.
441
450
http://ijrm.ir/browse.php?a_code=A-10-2671-1&slc_lang=en&sid=1
Marzie
Ghorbani
Rozhinaghorbani@yahoo.com