Tong Xian-Hong, Xu Bo, Zhang Yuan-Wei, Liu Yu-Sheng, Ma Chun-Hong
Institute of Immunology, Medical College of Shandong University, Ji'nan, China; Center for Reproductive Medicine, Anhui Provincial Hospital Affiliated with Anhui Medical University, Hefei, China.
Center for Reproductive Medicine, Anhui Provincial Hospital Affiliated with Anhui Medical University, Hefei, China.
PLoS One. 2014 Sep 4;9(9):e106706. doi: 10.1371/journal.pone.0106706. eCollection 2014.
During folliculogenesis, cumulus cells surrounding the oocyte differentiate into corona radiata cells (CRCs) and cumulus oophorus cells (COCs), which are involved in gonadal steroidogenesis and the development of germ cells. Several studies suggested that microRNAs (miRNAs) play an important regulatory role at the post-transcriptional level in cumulus cells. However, comparative miRNA profiles and associated processes in human CRCs and COCs have not been reported before. In this study, miRNA profiles were obtained from CRCs and COCs using next generation sequencing in women undergoing controlled ovarian stimulation for IVF. A total of 785 and 799 annotated miRNAs were identified in CRCs and COCs, while high expression levels of six novel miRNAs were detected both in CRCs and in COCs. In addition, different expression patterns in CRCs and COCs were detected in 72 annotated miRNAs. To confirm the miRNA profile in COCs and CRCs, quantitative real-time PCR was used to validate the expression of annotated miRNAs, differentially expressed miRNAs, and novel miRNAs. The miRNAs in the let-7 family were found to be involved in the regulation of a broad range of biological processes in both cumulus cell populations, which was accompanied by a large amount of miRNA editing. Bioinformatics analysis showed that amino acid and energy metabolism were targeted significantly by miRNAs that were differentially expressed between CRCs and COCs. Our work extends the current knowledge of the regulatory role of miRNAs and their targeted pathways in folliculogenesis, and provides novel candidates for molecular biomarkers in the research of female infertility.
在卵泡发生过程中，围绕卵母细胞的卵丘细胞分化为放射冠细胞（CRCs）和卵丘细胞（COCs），它们参与性腺类固醇生成和生殖细胞的发育。多项研究表明，微小RNA（miRNAs）在卵丘细胞的转录后水平发挥重要调节作用。然而，此前尚未报道过人类CRCs和COCs中miRNA的比较图谱及相关过程。在本研究中，通过下一代测序从接受体外受精控制性卵巢刺激的女性的CRCs和COCs中获得了miRNA图谱。在CRCs和COCs中分别鉴定出785个和799个注释的miRNAs，同时在CRCs和COCs中均检测到6个新miRNAs的高表达水平。此外，在72个注释的miRNAs中检测到CRCs和COCs中的不同表达模式。为了确认COCs和CRCs中的miRNA图谱，使用定量实时PCR验证注释的miRNAs、差异表达的miRNAs和新miRNAs的表达。发现let-7家族的miRNAs参与了两种卵丘细胞群体中广泛的生物学过程的调节，这伴随着大量的miRNA编辑。生物信息学分析表明，CRCs和COCs之间差异表达的miRNAs显著靶向氨基酸和能量代谢。我们的工作扩展了目前关于miRNAs及其靶向途径在卵泡发生中的调节作用的知识，并为女性不孕症研究中的分子生物标志物提供了新的候选物。
