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来曲唑诱导的大鼠多囊卵巢综合征模型子宫中微小RNA的表达改变

Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model.

作者信息

Li Chunjin, Chen Lu, Zhao Yun, Chen Shuxiong, Fu Lulu, Jiang Yanwen, Gao Shan, Liu Zhuo, Wang Fengge, Zhu Xiaoling, Rao Jiahui, Zhang Jing, Zhou Xu

机构信息

College of Animal Sciences, Jilin University, 5333 Xian Road, Changchun, Jilin 130062, People's Republic of China.

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

出版信息

Gene. 2017 Jan 20;598:20-26. doi: 10.1016/j.gene.2016.10.033. Epub 2016 Oct 21.

DOI:10.1016/j.gene.2016.10.033
PMID:27777110
Abstract

Polycystic ovary syndrome (PCOS) causes female subfertility with ovarian disorders and may be associated with increased rate of early-pregnancy failure. Rat PCOS models were established using letrozole to understand the uterine pathogenesis of PCOS. The differential expression of microRNAs (miRNAs) was observed in rat uterus with PCOS. After estrous cycles were disrupted, significantly abnormal ovarian morphology and hormone level were observed in rats with PCOS. A total of 148 miRNAs differentially expressed were identified in the uterus from the letrozole-induced rat model compared with the control. These miRNAs included 111 upregulated miRNAs and 37 downregulated miRNAs. The differential expression of miR-484, miR-375-3p, miR-324-5p, and miR-223-3p was further confirmed by quantitative reverse transcription polymerase chain reaction. Bioinformatic analysis showed that these four miRNAs were predicted to regulate a large number of genes with different functions. Pathway analysis supported that target genes of miRNAs were involved in insulin secretion and signaling pathways, such as wnt, AMPK, PI3K-Akt, and Ras. These data indicated that miRNAs differentially expressed in rat uterus with PCOS may be associated with PCOS pathogenesis in the uterus. Our findings can help clarify the mechanism of uterine defects in PCOS.

摘要

多囊卵巢综合征(PCOS)可导致女性因卵巢功能障碍而生育力低下,并可能与早期妊娠失败率增加有关。使用来曲唑建立大鼠PCOS模型,以了解PCOS的子宫发病机制。在患有PCOS的大鼠子宫中观察到了微小RNA(miRNA)的差异表达。在发情周期紊乱后,PCOS大鼠出现明显异常的卵巢形态和激素水平。与对照组相比,在来曲唑诱导的大鼠模型子宫中鉴定出总共148种差异表达的miRNA。这些miRNA包括111种上调的miRNA和37种下调的miRNA。通过定量逆转录聚合酶链反应进一步证实了miR-484、miR-375-3p、miR-324-5p和miR-223-3p的差异表达。生物信息学分析表明,这四种miRNA预计可调控大量具有不同功能的基因。通路分析支持miRNA的靶基因参与胰岛素分泌和信号通路,如wnt、AMPK、PI3K-Akt和Ras。这些数据表明,在患有PCOS的大鼠子宫中差异表达的miRNA可能与PCOS的子宫发病机制有关。我们的研究结果有助于阐明PCOS中子宫缺陷的机制。

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