基于血浆转录组学进行生精障碍无创诊断分子标志物筛选和临床评价的研究

项目名称： 基于血浆转录组学进行生精障碍无创诊断分子标志物筛选和临床评价的研究

项目编号： No.81471495

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 田永红

作者单位： 浙江大学

项目金额： 73万元

中文摘要： 临床上对男性不育症患者生精功能的最终诊断依赖于睾丸组织病理检查。但睾丸活检的创伤性及损伤生精功能的缺点，且精子发生具有局灶性和双侧睾丸差异性，故活组织检查准确性尚不够，故亟待发展更为准确、无创性的检查技术。无创性的血浆 cell-free mRNA 检查技术已在肿瘤及产前诊断领域得到了广泛研究和应用。我们前期研究发现血浆内存在多种精子发生特异表达基因的 mRNAs，其表达组合模式随睾丸病理类型的不同而异,即血浆 cell-free mRNA 表达谱与生精功能发生具有相关性。本研究拟采用基因表达芯片检测各睾丸病理类型患者血浆 cell-free mRNA 基因表达谱，利用基因差异表达及聚类分析等生物信息学技术，筛出各病理学类型特异表达基因（组）并进行临床验证，奠定血浆 cell-free mRNA做为判断睾丸生精功能的无创性检测的分子标志物的基础，探索正常人类精子发生和精子发生障碍分子机制。

中文关键词： 生精障碍；无创性诊断；游离信使核糖核酸；血浆；男性不育

英文摘要： Testis biopsy has been considered as the gold standard of judging spermatogenesis status in clinic. However, the invasiveness and spermatogenic function injury of testis biopsy are the obstacles in application. Also, the accuracy was damaged by focal and heterogeneity of spermatogenesis in testis. So, we need to develop more accurate and operable but non-invasive diagnosis techniques. Nowadays, noninvasive plasma cell-free mRNA diagnosis technology has been widely studied and applied to the field of tumor detection and prenatal diagnosis. In our previous study, specific expression of a variety spermatogenesis specific genes mRNAs had been detected in plasma and their expression patterns varied with the types of testicular pathology. On the basis of the results, plasma cell-free mRNA gene expression profiles in the infertile men will be detected by microarray tecnology with the classification of testicular pathology. Then the pathological type specific expression of the gene and/or gene clusters will be sieved out and the model for diagnosis be established by bioinformatics technology such as the differential gene expression, hierarchical cluster analysis and classification analysis etc. Afterwards, the technology for non-invasive diagnosis of spermatogenesis status by cell-free mRNA analysis in plasma shoud be validated to lay the foundation for clinical application. Furthermore,investigation for the molecular mechanism of normal spermatogenesis and/or spermatogenic dsfunction will be explored.

英文关键词： impaired spermatogenesis;noninvasive diagnosis;cell-free mRNA;blood plasma;male infertility