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

机译:来曲唑诱导的多囊卵巢综合征大鼠模型卵巢中microRNA的差异表达

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摘要

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.
机译:多囊卵巢综合征(PCOS)是一种复杂的异质内分泌疾病。为了了解PCOS的发病机制,我们建立了来曲唑诱导的PCOS大鼠模型,并进行了深度测序以筛选microRNA(miRNA)在PCOS大鼠和对照大鼠中的差异表达。我们观察了阴道涂片并检测了PCOS大鼠的卵巢病理改变和激素水平变化。深度测序表明,与对照组相比,来曲唑诱导的大鼠模型卵巢中共有129个miRNA差异表达,包括上调的49个miRNA和下调的80个miRNA。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,这四个miRNA被预测针对具有不同功能的大量基因。通路分析支持miRNA调节卵母细胞减数分裂,丝裂原激活的蛋白激酶(MAPK)信号传导,磷酸肌醇3激酶/ Akt(PI3K-Akt)信号传导,Rap1信号传导和Notch信号传导。这些数据表明,miRNA在大鼠PCOS模型中差异表达,而差异表达的miRNA参与PCOS的病因和病理生理。我们的发现将有助于鉴定miRNA作为PCOS的新型诊断标记和治疗靶标。

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