Cheraghi Ebrahim, Soleimani Mehranjani Malek, Shariatzadeh Seyed Mohammad Ali, Nasr Esfahani Mohammad Hossein, Alani Behrang
Department of Biology, Faculty of Sciences, University of Qom, Qom, Iran.
Department of Biology, Faculty of Science, Arak University, Arak, Iran.
Int J Fertil Steril. 2018 Jan;11(4):270-278. doi: 10.22074/ijfs.2018.5142. Epub 2017 Oct 12.
Paracrine disruption of growth factors in women with polycystic ovarian syndrome (PCOS) results in production of low quality oocyte, especially following ovulation induction. The aim of this study was to investigate the effects of metformin (MET), N-acetylcysteine (NAC) and their combination on the hormonal levels and expression profile of GDF-9, BMP-15 and c-kit, as hallmarks of oocyte quality, in PCOS patients.
This prospective randomized, double-blind, placebo controlled trial aims to study the effects of MET, NAC and their combination (MET+NAC) on expression of GDF-9, BMP-15 and c-kit mRNA in oocytes [10 at the germinal vesicle (GV) stage, 10 at the MI stage, and 10 at the MII stage from per group] derived following ovulation induction in PCOS. Treatment was carried out for six weeks, starting on the third day of previous cycle until oocyte aspiration. The expression of GDF9, BMP15 and c-kit were determined by quantitative real time polymerase chain reaction (RT-qPCR) and western blot analysis. Data were analyzed with one-way ANOVA.
The follicular fluid (FF) level of c-kit protein significantly decreased in the NAC group compared to the other groups. Significant correlations were observed between the FF soluble c-kit protein with FF volume, androstenedione and estradiol. The GDF-9 expression in unfertilized mature oocytes were significantly higher in the NAC group compared to the other groups (P<0.001). Similar difference was not observed between the MET, NAC+MET and control groups. The c-kit expression in unfertilized mature oocytes were significantly lower in the NAC group compared to the other groups (P<0.001). Similar difference was not observed between the MET, NAC+MET and control groups (Registration number: IRCT201204159476N1).
We concluded that NAC can improve the quality of oocytes in PCOS.
多囊卵巢综合征（PCOS）女性中生长因子的旁分泌破坏会导致产生低质量的卵母细胞，尤其是在排卵诱导后。本研究的目的是探讨二甲双胍（MET）、N-乙酰半胱氨酸（NAC）及其组合对PCOS患者激素水平以及作为卵母细胞质量标志的生长分化因子9（GDF-9）、骨形态发生蛋白15（BMP-15）和原癌基因c-kit表达谱的影响。
这项前瞻性随机、双盲、安慰剂对照试验旨在研究MET、NAC及其组合（MET+NAC）对PCOS患者排卵诱导后获得的卵母细胞（每组在生发泡期、减数分裂中期I和减数分裂中期II各10个）中GDF-9、BMP-15和c-kit mRNA表达的影响。治疗从上次月经周期的第三天开始，持续六周，直至卵母细胞抽吸。通过定量实时聚合酶链反应（RT-qPCR）和蛋白质免疫印迹分析测定GDF9、BMP15和c-kit的表达。数据采用单因素方差分析。
与其他组相比，NAC组卵泡液（FF）中c-kit蛋白水平显著降低。FF中可溶性c-kit蛋白与FF体积、雄烯二酮和雌二醇之间存在显著相关性。与其他组相比，NAC组未受精成熟卵母细胞中GDF-9的表达显著更高（P<0.001）。MET组、NAC+MET组和对照组之间未观察到类似差异。与其他组相比，NAC组未受精成熟卵母细胞中c-kit的表达显著更低（P<0.001）。MET组、NAC+MET组和对照组之间未观察到类似差异（注册号：IRCT201204159476N1）。
我们得出结论，NAC可改善PCOS患者的卵母细胞质量。
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