Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model
Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model
复制标题
来曲唑诱导的大鼠 PCOS 模型子宫中 miRNA 表达的改变
DOI：
10.1016/j.gene.2016.10.033
复制
发表时间：
2017-01-20
期刊：
影响因子：
3.5
通讯作者：
Zhou, Xu
中科院分区：
文献类型：
--
作者：
Li, Chunjin;Chen, Lu;Zhou, Xu
多囊卵巢综合征（PCOS）导致女性生育力低下，卵巢功能紊乱，可能与早孕失败率增加有关。用来曲唑建立大鼠PCOS模型，探讨PCOS的子宫发病机制。microRNAs（miRNAs）在PCOS大鼠子宫中的表达存在差异。PCOS大鼠动情周期中断后，卵巢形态和激素水平明显异常。与对照组相比，来曲唑诱导的大鼠模型的子宫中共鉴定出148个差异表达的miRNA。这些miRNAs包括111个上调的miRNAs和37个下调的miRNAs。通过定量逆转录聚合酶链反应进一步证实miR-484、miR-375- 3 p、miR-324- 5 p和miR-223- 3 p的差异表达。生物信息学分析表明，这4种miRNAs调控着大量不同功能的基因。通路分析支持miRNAs靶基因参与胰岛素分泌和信号通路，如wnt、AMPK、PI 3 K-Akt和Ras。这些数据表明，差异表达的miRNAs在PCOS大鼠子宫可能与PCOS的发病机制在子宫。我们的研究结果有助于阐明PCOS子宫缺陷的机制。(C)2016由Elsevier B. V.出版
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. (C) 2016 Published by Elsevier B.V.