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控制性卵巢刺激过程中人类卵泡液中与多囊卵巢综合征相关的不同蛋白质表达模式。

Different protein expression patterns associated with polycystic ovary syndrome in human follicular fluid during controlled ovarian hyperstimulation.

作者信息

Dai Guo, Lu Guangxiu

机构信息

Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha 410078, People's Republic of China.

出版信息

Reprod Fertil Dev. 2012;24(7):893-904. doi: 10.1071/RD11201.

Abstract

Polycystic ovary syndrome (PCOS) is one of the most common causes of anovulatory infertility, affecting 5-10% of females during their reproductive life. Currently the pathology of PCOS is largely unknown. To identify the differential protein expression in follicular fluids from PCOS and normal subjects during controlled ovarian hyperstimulation, we performed an initial proteomic study including two-dimensional gel electrophoresis (2DE) analysis and mass spectroscopy, and confirmed results by western blot. Thirty-two protein spots were shown to be significantly differentially expressed between PCOS and normal follicular fluids, of which 20 unique proteins were identified to be associated with cellular metabolism and physiological processes; 13 of these proteins were upregulated while seven were downregulated in PCOS follicular fluids. Western blotting analyses confirmed the differential expressions for three randomly selected proteins, i.e. upregulated α1-antitrypsin, apolipoprotein A-I and transferrin in follicular fluid from PCOS patients than normal controls. Furthermore, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses revealed that mRNA levels of serine palmitoyltransferase 2, serine/threonine-protein kinase male germ cell-associated kinase (MAK) and DNA damage-regulated autophagy modulator protein 2 decreased significantly in granulosa cells of PCOS patients compared with normal samples. These results increase our understanding of PCOS and the identified genes may serve as candidate biomarkers to develop diagnostic and therapeutic tools.

摘要

多囊卵巢综合征(PCOS)是无排卵性不孕最常见的原因之一,在育龄期女性中发病率为5%-10%。目前,PCOS的发病机制尚不清楚。为了鉴定控制性卵巢刺激过程中PCOS患者和正常受试者卵泡液中的差异蛋白表达,我们开展了一项初步的蛋白质组学研究,包括二维凝胶电泳(2DE)分析和质谱分析,并通过蛋白质免疫印迹法进行结果验证。结果显示,PCOS患者和正常受试者的卵泡液中有32个蛋白点存在显著差异表达,其中20种独特蛋白被鉴定与细胞代谢和生理过程相关;PCOS卵泡液中,13种蛋白表达上调,7种蛋白表达下调。蛋白质免疫印迹分析证实了随机选择的3种蛋白的差异表达,即PCOS患者卵泡液中α1-抗胰蛋白酶、载脂蛋白A-I和转铁蛋白的表达高于正常对照。此外,半定量逆转录-聚合酶链反应(RT-PCR)分析显示,与正常样本相比,PCOS患者颗粒细胞中丝氨酸棕榈酰转移酶2、丝氨酸/苏氨酸蛋白激酶雄性生殖细胞相关激酶(MAK)和DNA损伤调节自噬调节蛋白2的mRNA水平显著降低。这些结果加深了我们对PCOS的理解,所鉴定的基因可能作为开发诊断和治疗工具的候选生物标志物。

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