New Cellularand Molecular Biotechnology Journal

other بررسیِ اثرِ متفورمین بر بیانِ پروتئینِ IGF-1 و IGF-2 در سرم، مایعِ فولیکولی (FF) و سلول‌های کومولوس (CCs) در بیمارانِ PCOS تحتِ تزریقِ داخلِ سیتوپلاسمیِ اسپرم (ICSI) The Role of Metformin in Modulating IGF1 and IGF2 Protein Expression in Patients with Polycystic Ovary Syndrome Undergoing Intracytoplasmic Sperm Injection جنین شناسی Embryology مقاله پژوهشی Research Article زمینه و هدف: این مطالعه با هدفِ بررسیِ تأثیرِ متفورمین بر بیانِ پروتئین‌های IGF1 و IGF2 در سرم، مایعِ فولیکولی (FF) و سلول‌های کومولوس (CCs) زنانِ مبتلا به سندرمِ تخمدانِ پلی‌کیستیک (PCOS1)، تحتِ درمانِ تزریقِ داخلِ سیتوپلاسمیِ اسپرم انجام شد. مواد و روش‌ها: در این مطالعه 90 زن تحتِ ICSI در سه گروه شاملِ کنترل،  PCOSو PCOS دریافت‌کنندۀ متفورمین بررسی شدند. سطوحِ پروتئین‌های IGF1 و IGF2 در نمونه‌های سرم، FF و CCs با استفاده از روشِ ELISA اندازه‌گیری شد. نتایج: در گروهِ PCOS، سطحِ IGF1 در سرم و FF به‌‌طورِ معنی‌داری بیشتر از گروهِ کنترل بود، درحالی‌که در CCs کاهشِ معنی‌داری مشاهده شد(p < 0.001). درمان با متفورمین موجبِ کاهشِ سطحِ سرمیِ IGF1  و افزایشِ معنی‌دارِ آن در CCs شد (p < 0.001)، امّا تغییری در سطحِ FF ایجاد نکرد. همچنین، سطحِ IGF2 در سرم، FF و CCs گروهِ PCOS نسبت به گروهِ کنترل افزایشِ معنی‌داری داشت (به‌ترتیب p < 0.001, <a name="_Hlk231821911">p < 0.001</a>, p < 0.01). متفورمین سطحِ سرمیِ IGF2 را کاهش داد (p < 0.001)، امّا غلظتِ آن در FF و CCs در مقایسه با گروهِ کنترل همچنان بالا باقی ماند (p < 0.001) و در CCs نسبت به گروهِ PCOS درمان‌نشده افزایشِ بیشتری نشان داد(p < 0.01). در هر دو گروهِPCOS  و +PCOSمتفورمین، سطحِ IGF2 در FF و CCs به‌طور معنی‌داری بالاتر از سرم بود (p < 0.001). نتیجه‌گیری: متفورمین احتمالاً از طریقِ تعدیلِ سیستمِ IGF و افزایشِ بیانِ موضعیِ IGF1 و IGF2 در محیطِ فولیکولی، شرایطِ مناسب‌تری برای رشدِ فولیکول و بهبودِ نتایجِ تولیدمثلی در زنانِ مبتلا به PCOS  فراهم می‌کند. <div style="text-align: justify;">| Extended Abstract Background and Aim: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age and is associated with ovulatory dysfunction, infertility, hyperandrogenism, insulin resistance, and metabolic abnormalities. These disturbances may adversely affect follicular development and oocyte maturation. The insulin-like growth factor (IGF) system, particularly IGF-1 and IGF-2, plays an important role in ovarian function, granulosa cell activity, folliculogenesis, and oocyte development. Alterations in IGF signaling may contribute to the abnormal ovarian microenvironment observed in women with PCOS. Metformin, an insulin-sensitizing agent commonly prescribed for PCOS, may influence this system by improving metabolic and endocrine regulation. However, its effects on IGF-1 and IGF-2 protein levels in different biological compartments remain incompletely understood. This study aimed to investigate the association between metformin treatment and IGF-1 and IGF-2 protein levels in serum, follicular fluid (FF), and cumulus cells (CCs) of women with PCOS undergoing intracytoplasmic sperm injection (ICSI). Materials and Methods: This case–control study included 90 women aged 20–35 years undergoing ICSI at Sarem Hospital, Tehran, Iran. Participants were divided into three groups: healthy controls (n = 30), women with untreated PCOS (n = 30), and women with PCOS receiving metformin treatment (n = 30). Samples were collected between November 2021 and March 2023. Metformin was prescribed by fertility specialists, with the daily dose gradually increased from 500 mg during the first week to 2,000 mg during the fourth week. Serum samples were collected before follicular aspiration. Follicular fluid was obtained during ultrasound-guided oocyte retrieval, and blood-contaminated samples were excluded. Cumulus cells were isolated from cumulus–oocyte complexes using hyaluronidase treatment and mechanical separation. IGF-1 and IGF-2 protein concentrations in serum, FF, and CCs were measured using enzyme-linked immunosorbent assays (ELISA). Statistical analyses were performed using SPSS version 25. One-way analysis of variance followed by Tukey’s post hoc test was used for group comparisons, and p < 0.05 was considered statistically significant. Results: IGF-1 protein levels showed distinct patterns across biological compartments. In women with untreated PCOS, IGF-1 concentrations were significantly higher in serum and FF but significantly lower in CCs than in controls (p < 0.001). In the metformin-treated group, serum IGF-1 levels were significantly lower than those in untreated PCOS, whereas FF levels remained largely unchanged. Conversely, IGF-1 levels in CCs were significantly higher in the metformin-treated group than in the untreated PCOS group (p < 0.001). IGF-2 concentrations were significantly elevated in serum, FF, and CCs in untreated PCOS compared with controls. Metformin treatment significantly reduced serum IGF-2 levels relative to untreated PCOS. Nevertheless, IGF-2 concentrations in FF and CCs remained significantly higher than those in controls (p < 0.001). Furthermore, IGF-2 levels in CCs were significantly higher in the metformin-treated group than in the untreated PCOS group (p < 0.01). These findings demonstrate that the changes associated with metformin differed between systemic circulation and the local ovarian environment. The findings indicate that PCOS is associated with compartment-specific alterations in IGF-1 and IGF-2 protein levels in serum, follicular fluid, and cumulus cells. Metformin treatment was associated with reduced circulating IGF-1 and IGF-2 levels and altered protein profiles in cumulus cells, while elevated IGF-2 levels persisted in follicular fluid and cumulus cells. Conclusion: These observations suggest that the systemic and local ovarian components of the IGF system may respond differently to metformin treatment. The findings provide additional insight into the potential relationship between metabolic regulation and ovarian growth-factor signaling in women with PCOS undergoing ICSI. However, because of the observational design and relatively short treatment period, causal effects of metformin cannot be established. Further prospective studies with larger sample sizes, longer treatment periods, and direct assessment of oocyte quality, embryo development, implantation, and pregnancy outcomes are required to clarify the clinical significance of these changes.</div> تخمدان پلی‌کیستیک , پروتئینِ IGF1 , پروتئینِ IGF2 , تزریقِ داخلِ سیتوپلاسمیِ اسپرم PCOS, IGF1 Protein, IGF2 Protein, ICSI 29 41 http://ncmbjpiau.ir/browse.php?a_code=A-10-18-6&slc_lang=other&sid=1 Zahra Karami زهرا کرمی No Department of Biology, Pa. C., Islamic Azad University, Parand, Iran گروه زیست‌شناسی، واحد پرند، دانشگاه آزاد اسلامی، پرند، ایران Parvin Khodarahmi پروین خدارحمی Yes Department of Biology, Pa. C., Islamic Azad University, Parand, Iran گروه زیست‌شناسی، واحد پرند، دانشگاه آزاد اسلامی، پرند، ایران Farzaneh Tafvizi فرزانه تفویضی No 1.Department of Biology, Pa. C., Islamic Azad University, Parand, Iran 2-Department of Chemical and Biological Technologies, CT.C, Islamic Azad University, Tehran, Iran 1.گروه زیست‌شناسی، واحد پرند، دانشگاه آزاد اسلامی، پرند، ایران 2- گروه فناوری های شیمی-زیستی، واحد تهران مرکزی، دانشگاه آزاد اسلامی، تهران، ایران Marefat Ghaffari-Novin معرفت غفاری نوین No - Department of Biology and Anatomical Science, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran گروه زیست‌شناسی و علوم تشریحی، دانشکدۀ پزشکی، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران