en مواجهه پیش از تولد با یک دوز تستوسترون کیفیت تخمک و رویان را در موش‌های صحرایی در دوران بزرگسالی به طور منفی تحت تأثیر قرار می دهد: یک مطالعه تجربی Reproductive Endocrinology 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:">مواجهه با آندروژن مازاد در دوره پیش از تولد می‌تواند بر محور هیپوتالاموس-هیپوفیز-تخمدان در جنین در حال رشد تأثیر منفی بگذارد و به طور بالقوه منجر به اختلال عملکرد طولانی مدت سیستم تولید&shy;مثلی در مراحل بعدی زندگی 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:">هدف ما بررسی این بود که آیا مواجهه پیش از تولد با یک دوز تستوسترون می‌تواند بر سیستم تولید&shy;مثلی، به ویژه کیفیت تخمک و رویان، و بیان ژن فاکتور تمایز رشد-9 </span></span><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">(</span></span><i><span dir="LTR" style="font-size:10.0pt">GDF-9</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">)</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در تخمدان موش</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:">های صحرایی در دوران بزرگسالی تأثیر بگذارد یا خیر.</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 تجربی، موش‌های صحرایی ویستار باردار (13-12 هفته، وزن بدن 10 </span></span><span lang="FA" style="font-size:10.0pt">&plusmn;</span> <span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">185 گرم) در گروه تجربی (تعداد </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:"> 5 سر) در روز 20 بارداری به صورت زیر جلدی تستوسترون آزاد (5 میلی‌گرم)، و گروه شاهد (تعداد </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:"> 5 سر) فقط حلال دریافت کردند. زاده&shy;های هر 2 گروه از نظر کیفیت تخمک و جنین (ضخامت لایه شفاف، تعداد لقاح طبیعی، تعداد جنین&shy;های دو سلولی و میزان توقف جنین) و بیان تخمدانی ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">GDF-9</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در بزرگسالی مورد بررسی قرار گرفتند. </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:">افزایش معنی‌داری در ضخامت زونا پلوسیدا (02/0 </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 موش&shy;های صحرایی که در دوره پیش از تولد در معرض آندروژن قرار گرفته بودند در مقایسه با گروه کنترل مشاهده شد. با این حال، تعداد لقاح طبیعی و تعداد رویان&shy;های دو سلولی در موش&shy;های صحرایی که در دوره پیش از تولد در معرض آندروژن قرار گرفته بودند در مقایسه با گروه کنترل کاهش معنی&shy;داری نشان داد (007/0 </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:"> و 01/0 </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:">، به ترتیب</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">). علاوه بر این، میزان توقف رویان در موش&shy;های صحرایی که در دوره پیش از تولد در معرض آندروژن قرار گرفته بودند در مقایسه با گروه کنترل بیشتر بود (004/0 </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:">). هیچ تفاوت معنی‌داری در بیان ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">GDF-9</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در تخمدان موش&shy;های صحرایی که در دوره پیش از تولد در معرض آندروژن قرار گرفته بودند در مقایسه با گروه کنترل مشاهده نشد.</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial",sans-serif"></span></span></span></span></span></span></span><br> <b><span dir="RTL" lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتیجه&shy; گیری:</span></span></b> <span dir="RTL" lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مواجهه با یک دوز تستوسترون در دوره پیش از تولد در طول یک دوره بحرانی از تکامل جنین، به طور قابل توجهی کیفیت تخمک و رویان را در موش‌های صحرایی بالغ مختل می‌کند. مطالعات بیشتر برای اعتبارسنجی این یافته‌ها و روشن شدن مکانیسم‌های مولکولی و فیزیولوژیکی زمینه‌ای مورد نیاز است.</span></span></div> <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Background:</span></span></b><span lang="EN" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> Prenatal exposure to excess androgen can adversely affect the hypothalamic-pituitary-ovarian axis in the developing fetus</span></span><span style="font-size:12.0pt"><span style="background:white"><span new="" roman="" style="font-family:" times="">,</span></span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> potentially leading to long-term reproductive system dysfunction in later life. </span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Objective: </span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">We aimed to investigate whether prenatal exposure to a single dose of testosterone can affect the reproductive system, especially oocyte and embryo quality, and the ovarian </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">expression of growth differentiation factor-9 (<i>GDF-9</i>) gene</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> in rats during adulthood</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">.</span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Materials and Methods:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> In this experimental study, pregnant Wistar rats (12-13 wk, 185 &plusmn; 10 gr) in the experimental group (n = 5) </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">subcutaneously</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> received free testosterone (5 mg) on the 20^th day of pregnancy, whereas controls received only solvent (n = 5). The offspring were evaluated for oocyte and embryo quality (</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">zona pellucida thickness</span></span><span 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=""> number of normal fertilization</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">, number of 2-cell embryos, and embryo arrest rate</span></span><span 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=""> and</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> ovarian </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">expression of <i>GDF-9</i> gene during adulthood. </span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="font-family:Calibri,sans-serif"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Results:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> A significant increase was observed in the zona pellucida thickness (p = 0.02)</span></span> <span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">in </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">prenatally-androgenized (PNA)</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> rats compared to controls. However, </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">reductions in</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> the number of normal fertilization</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> and 2-cell embryos </span></span><span 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 = 0.007, p = 0.01, respectively) </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">in </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">PNA</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> rats compared to controls</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> were observed. Furthermore, embryo arrest rate in PNA rats was significantly higher than in controls (p = 0.004).</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> No significant difference was observed in the </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">ovarian expression of<i> GDF-9</i> gene </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">in PNA rats compared to controls. </span></span><b><span style="font-size:12.0pt"><span style="font-family:"Times New Roman",serif"></span></span></b></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span style="font-family:Calibri,sans-serif"><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="">Prenatal</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> exposure to a single dose of testosterone </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">during</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> a critical </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">window</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> of fetal development </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">significantly impairs </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">oocyte and embryo quality</span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> in adult rats. Further studies </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">are needed to validate </span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">these findings and to elucidate the underlying molecular and physiological mechanisms.</span></span></span></span></span></span></div> <br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span sans-serif="" style="font-family:Calibri,"><span style="font-size:12.0pt"><span style="font-family:"Times New Roman","serif""></span></span></span></span></span></span> آندروژن, تخمک, جنین, GDF-9, موش صحرایی. Androgen, Oocyte, Embryo, Growth differentiation factor-9, Rat. 647 658 http://ijrm.ir/browse.php?a_code=A-10-1861-4&slc_lang=en&sid=1 Elahe Sadeghian Bakhi pardisiran22@yahoo.com 0000-0002-4258-5401 No Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran. Nasim Hayati Roodbari nasimhayati@yahoo.com 0009-0008-8785-3255 No Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran. Morteza Anvari moanvari@yahoo.com 0000-0003-3114-9513 No Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Fahimeh Ramezani Tehrani ramezani@endocrine.ac.ir; fah.tehrani@gmail.com; framezan@postharvard.edu 0000-0002-4609-065X Yes Reproductive Endocrinology Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.