弱精症、精子畸形症及正常男性精子的多种RNA表达谱的构建与分析

项目名称： 弱精症、精子畸形症及正常男性精子的多种RNA表达谱的构建与分析

项目编号： No.81200464

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 谢兰

作者单位： 清华大学

项目金额： 23万元

中文摘要： 弱精症和精子畸形症是临床上常见的男性不育疾病，而目前人们对于两种疾病的病因及发生机理还缺乏全面而系统的认识。成熟精子中存在着少量的各种形式的RNA，然而对这些转录子的功能却有待深入挖掘和阐明。本课题旨在利用实验室自主研发的多种高通量生物芯片平台，全面构建正常男性、弱精症、精子畸形症患者的精子的mRNA、miRNA、长链非编码RNA表达谱并找到在弱精症、精子畸形症患者的精子中异常表达的mRNA、miRNA、长链非编码RNA。在此基础上，通过生物信息学的方法深入挖掘多种RNA的调控关系网络并寻找可能有重要意义的节点，并对关键性的靶分子进行realtimePCR验证。通过全面建立两种不同疾病及健康状态下精子mRNA、miRNA、长链非编码RNA表达谱，可以进一步揭示精子发生过程中的异常事件和致病机理，丰富对于精子中非编码RNA的表达情况和功能的认识，也可能为未来的男性不育诊断提供新的生物标志物。

中文关键词： 弱精症；精子畸形症；基因表达谱；微小RNA；长链非编码RNA

英文摘要： Asthenozoospermia and teratozoospermia are both major causes of infertility or reduced fertility in men, while the etiology and pathogenic mechanisms of the two diseases remain to be explored. The presence of different RNA populations in human ejaculate spermatozoa is well established, yet little is known of the functional significance of these transcripts. This project aims to combine a variety of independently-developed high-throughput biochip platforms, to construct and analyze the mRNA profiles, miRNA profiles and long non-coding RNA profiles of spermatozoa from normal fertile men, asthenozoospermic patients and teratozoospermic patients. Also, we hope to characterize the differentially expressed mRNAs, miRNAs and lncRNAs in the sperm cells of asthenozoospermic or teratozoospermic patients compared with control fertile men. Through the following bioinformatics analysis, we anticipate the construction of a regulatory network of different RNA populations and the discovery of some novel critical target molecules. Realtime PCR validation will be performed for the key target molecules. Establishing the mRNA profiles of sperm from two different infertility-related diseases and normal fertile men, will reveal the significant events occuring during spermatogenesis. The establishment of the miRNA expression profiles

英文关键词： asthenozoospermia；teratozoospermia；gene expression profiling；miRNA；long non-coding RNA