Li Jingyu, Liu Dongyun, Wang Jiang, Deng Huali, Luo Xiu, Shen Xiaoli, Huan Yanjun, Huang Guoning, Ye Hong
Chongqing Reproductive and Genetics Institute, Yu Zhong District, Chongqing, China.
College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, China.
Oncotarget. 2017 Oct 26;8(60):102428-102436. doi: 10.18632/oncotarget.22096. eCollection 2017 Nov 24.
Genetic factors in endometrium are likely to be involved in the embryo implantation failure (IF), one of the major limiting factors in the success of fertilization (IVF). In this study, we aimed to identify critical genes from the transcriptional profile for the establishment of the endometrial receptivity which supporting the normal pregnancy. Three GEO datasets, including 12 samples of IF and 12 samples of controls, were used for the meta-analysis. We identified 182 different expression genes (DEGs) by comparing IF with controls and present here the successful clustering according to sample type, not by the origin. The gene ontology (GO) enriched analysis demonstrated the significant downregulation in activation and regulation of inflammatory and immune response in IF patients. Furthermore, network analysis of down-regulated genes identified the significant hub genes containing (growth arrest and DNA damage inducible alpha, Degree = 77), (granzyme B, Degree = 38) and (NLR family pyrin domain containing 2, Degree = 37). The lower expression of , related to inflammatory responses with the most degree in the network, was validatied by other GEO data. Besides, it was confirmed that the could act as a predictor for pregnancy after IVF (AUC = 87.93%; sensitivity, 60.00%; specificity, 91.30% ). Our meta-analysis will help us to better understand the molecular regulation of endometrial receptivity, and guiding further line of treatment for IF during IVF.
子宫内膜中的遗传因素可能与胚胎着床失败（IF）有关，胚胎着床失败是体外受精（IVF）成功的主要限制因素之一。在本研究中，我们旨在从转录谱中识别关键基因，以建立支持正常妊娠的子宫内膜容受性。三个GEO数据集，包括12个IF样本和12个对照样本，用于荟萃分析。通过将IF与对照进行比较，我们鉴定出182个差异表达基因（DEG），并在此展示了根据样本类型而非来源进行的成功聚类。基因本体（GO）富集分析表明，IF患者的炎症和免疫反应激活及调节存在显著下调。此外，对下调基因的网络分析确定了重要的枢纽基因，包括生长停滞和DNA损伤诱导α（Degree = 77）、颗粒酶B（Degree = 38）和含NLR家族pyrin结构域2（Degree = 37）。网络中与炎症反应相关程度最高的的低表达通过其他GEO数据得到验证。此外，证实了可作为IVF后妊娠的预测指标（AUC = 87.93%；敏感性，60.00%；特异性，91.30%）。我们的荟萃分析将有助于我们更好地理解子宫内膜容受性的分子调节，并指导IVF期间IF的进一步治疗方案。
