Disrupted gene pattern in patients with repeated in vitro fertilization (IVF) failure
Disrupted gene pattern in patients with repeated in vitro fertilization (IVF) failure
复制标题
DOI：
10.1093/humrep/dep193
复制
发表时间：
2009-10-01
影响因子：
6.1
通讯作者：
Reich, Reuven
中科院分区：
文献类型：
--
作者：
Koler, Moriah;Achache, Hanna;Reich, Reuven
重复着床失败(RIF)是人类辅助生殖治疗中的一个严重障碍，为了确定RIF患者的整体基因谱，对12例育龄妇女和20例RIF患者在周期第21天采集的子宫内膜标本进行了基因芯片分析。用实时定量聚合酶链式反应对细胞周期蛋白E2、Slug、Dickkopf同系物1(Dkk1)、淋巴增强因子1(LEF1)和分泌型卷曲相关蛋白1(SFRP1)进行验证。基因芯片分析发现RIF患者中有313个基因表达水平改变。在这些基因中，288个基因(92%)下调，只有25个基因(8%)上调。对下调基因的生物学途径进行分类，揭示了细胞周期、Wnt信号和细胞黏附途径。实时定量聚合酶链式反应验证细胞周期蛋白E2、SFRP1和LEF1在RIF-IVF患者中的表达水平显著低于生育女性。此外，两个上调的基因slug和Dkk1也得到了验证。有趣的是，下调的基因中约有8%依赖于雌激素。蛋白质印迹显示该蛋白在RIF组低表达，基因芯片分析显示RIF患者子宫内膜多种基因表达发生改变，包括细胞周期、Wnt信号转导和细胞黏附途径。
Repeated implantation failure (RIF) is a severe obstacle in human assisted reproduction treatment.Aiming to identify global gene profile in RIF patients, gene-array analyses were performed on endometrial samples collected on day 21 of the cycle from fertile women (n = 12) and from RIF patients (n = 20). Validation of cyclin E2, Slug, dickkopf homolog 1 (DKK1), lymphoid enhancer-binding factor 1 (LEF1) and secreted frizzled-related protein 1 (SFRP1) was carried out by real-time PCR.Gene-array analysis revealed 313 genes exhibiting modified expression levels in RIF patients. Of these, 288 genes (92%) were down-regulated and only 25 genes (8%) were up-regulated. Classification of the down-regulated genes to biological pathways revealed cell cycle, Wnt signaling and cellular adhesion pathways. Real-time PCR validation of cyclin E2, SFRP1 and LEF1 showed significantly lower expression levels in RIF-IVF patients as compared with fertile women. In addition, two up-regulated genes, Slug and DKK1, were also validated. Interestingly, about 8% of the down-regulated genes were estrogen-dependent. Western blot of estrogen receptor alpha revealed low expression of this protein in the RIF group.The evaluation of the endometrium of RIF patients by gene array analysis demonstrates that the expression of various genes is altered, including those belonging to the cell cycle, Wnt signaling and cellular adhesion pathways.