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多囊卵巢综合征患者颗粒细胞中与MAPK/ERK信号通路相关的差异表达基因的功能微阵列分析

Functional microarray analysis of differentially expressed genes in granulosa cells from women with polycystic ovary syndrome related to MAPK/ERK signaling.

作者信息

Lan Chen-Wei, Chen Mei-Jou, Tai Kang-Yu, Yu Danny Cw, Yang Yu-Chieh, Jan Pey-Shynan, Yang Yu-Shih, Chen Hsin-Fu, Ho Hong-Nerng

机构信息

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University Taipei, Taiwan.

出版信息

Sci Rep. 2015 Oct 13;5:14994. doi: 10.1038/srep14994.

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Although its aetiology and pathogenesis remain unclear, recent studies suggest that the dysfunction of granulosa cells may partly be responsible. This study aimed to use cDNA microarray technology to compare granulosa cell gene expression profiles in women with and without PCOS to identify genes that may be aetiologically implicated in the pathogenesis of PCOS. The study cohort included 12 women undergoing in vitro fertilization, six with PCOS and six without PCOS. Differential gene expression profiles were classified by post-analyses of microarray data, followed by western blot analyses to confirm the microarray data of selected genes. In total, 243 genes were differentially expressed (125 upregulated and 118 downregulated) between the PCOS and non-PCOS granulosa cells. These genes are involved in reproductive system development, amino acid metabolism and cellular development and proliferation. Comparative analysis revealed genes involved in the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) signaling pathways. Western blot analyses confirmed that mitogen-activated protein kinase kinase kinase 4 and phospho-ERK1/2 were decreased in PCOS granulosa cells. This study identified candidate genes involved in MAPK/ERK signaling pathways that may influence the function of granulosa cells in PCOS.

摘要

多囊卵巢综合征(PCOS)是育龄期女性最常见的内分泌紊乱疾病。尽管其病因和发病机制尚不清楚,但最近的研究表明,颗粒细胞功能障碍可能是部分原因。本研究旨在利用cDNA微阵列技术比较患有和未患有PCOS的女性颗粒细胞基因表达谱,以鉴定可能在PCOS发病机制中具有病因学意义的基因。研究队列包括12名接受体外受精的女性,其中6名患有PCOS,6名未患有PCOS。通过对微阵列数据进行分析后分类差异基因表达谱,随后进行蛋白质印迹分析以确认所选基因的微阵列数据。在PCOS和非PCOS颗粒细胞之间,总共243个基因存在差异表达(125个上调和118个下调)。这些基因参与生殖系统发育、氨基酸代谢以及细胞发育和增殖。比较分析揭示了参与丝裂原活化蛋白激酶/细胞外调节激酶(MAPK/ERK)信号通路的基因。蛋白质印迹分析证实,PCOS颗粒细胞中丝裂原活化蛋白激酶激酶激酶4和磷酸化ERK1/2减少。本研究鉴定出参与MAPK/ERK信号通路的候选基因,这些基因可能影响PCOS中颗粒细胞的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2909/4602237/0f1045cd649b/srep14994-f1.jpg

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