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来曲唑诱导的多囊卵巢综合征大鼠模型卵巢中微小RNA的差异表达

Differential Expression of microRNAs in the Ovaries from Letrozole-Induced Rat Model of Polycystic Ovary Syndrome.

作者信息

Li Dandan, Li Chunjin, Xu Ying, Xu Duo, Li Hongjiao, Gao Liwei, Chen Shuxiong, Fu Lulu, Xu Xin, Liu Yongzheng, Zhang Xueying, Zhang Jingshun, Ming Hao, Zheng Lianwen

机构信息

1 Reproductive Medical Center, The Second Hospital of Jilin University , Changchun, People's Republic of China .

2 Department of Gynecological Oncology, Tumor Hospital of Jilin Province , Changchun, People's Republic of China .

出版信息

DNA Cell Biol. 2016 Apr;35(4):177-83. doi: 10.1089/dna.2015.3145. Epub 2016 Jan 8.

Abstract

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder. To understand the pathogenesis of PCOS, we established rat models of PCOS induced by letrozole and employed deep sequencing to screen the differential expression of microRNAs (miRNAs) in PCOS rats and control rats. We observed vaginal smear and detected ovarian pathological alteration and hormone level changes in PCOS rats. Deep sequencing showed that a total of 129 miRNAs were differentially expressed in the ovaries from letrozole-induced rat model compared with the control, including 49 miRNAs upregulated and 80 miRNAs downregulated. Furthermore, the differential expression of miR-201-5p, miR-34b-5p, miR-141-3p, and miR-200a-3p were confirmed by real-time polymerase chain reaction. Bioinformatic analysis revealed that these four miRNAs were predicted to target a large set of genes with different functions. Pathway analysis supported that the miRNAs regulate oocyte meiosis, mitogen-activated protein kinase (MAPK) signaling, phosphoinositide 3-kinase/Akt (PI3K-Akt) signaling, Rap1 signaling, and Notch signaling. These data indicate that miRNAs are differentially expressed in rat PCOS model and the differentially expressed miRNA are involved in the etiology and pathophysiology of PCOS. Our findings will help identify miRNAs as novel diagnostic markers and therapeutic targets for PCOS.

摘要

多囊卵巢综合征(PCOS)是一种复杂的异质性内分泌疾病。为了解PCOS的发病机制,我们建立了来曲唑诱导的PCOS大鼠模型,并采用深度测序技术筛选PCOS大鼠和对照大鼠中微小RNA(miRNA)的差异表达。我们观察了PCOS大鼠的阴道涂片,并检测了其卵巢病理改变和激素水平变化。深度测序结果显示,与对照组相比,来曲唑诱导的大鼠模型卵巢中共有129种miRNA表达存在差异,其中49种miRNA上调,80种miRNA下调。此外,通过实时聚合酶链反应证实了miR-201-5p、miR-34b-5p、miR-141-3p和miR-200a-3p的差异表达。生物信息学分析表明,这四种miRNA预计靶向大量具有不同功能的基因。通路分析支持这些miRNA调节卵母细胞减数分裂、丝裂原活化蛋白激酶(MAPK)信号通路、磷脂酰肌醇3激酶/蛋白激酶B(PI3K-Akt)信号通路、Rap1信号通路和Notch信号通路。这些数据表明,miRNA在大鼠PCOS模型中存在差异表达,且差异表达的miRNA参与了PCOS的病因学和病理生理学过程。我们的研究结果将有助于将miRNA鉴定为PCOS的新型诊断标志物和治疗靶点。

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