灵长类特异蛋白TDRG1在人成熟精子中的功能及其与弱精症相关性

项目名称： 灵长类特异蛋白TDRG1在人成熟精子中的功能及其与弱精症相关性

项目编号： No.81501317

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 陈厚仰

作者单位： 江西省妇幼保健院

项目金额： 18万元

中文摘要： 弱精症是男性不育的常见病因，可能和睾丸特异性基因表达异常有关。TDRG1(Testis Development Related Gene 1)是申请人参与鉴定的灵长类睾丸特异性基因。申请人最近发表的研究结果证实TDRG1存在于正常人成熟精子尾部胞浆中。更重要的是，在我们已检测的30例弱精症精子中，60%样品的TDRG1含量明显下降。这些结果提示TDRG1参与调控精子运动，但其在人成熟精子中的具体功能及其作用机制尚待阐明。本项目拟：1）临床大样本筛查TDRG1与弱精症的相关性；2）在我们已证实穿膜肽TAT能将外源蛋白导入精子胞浆的基础上，利用穿膜肽将TDRG1重组蛋白或抗体分别导入弱精症或正常人精子中，系统研究TDRG1在人成熟精子中的功能；3）探讨TDRG1在成熟人精子中的作用机制。本课题可能发现精子功能调控新途径，并对发展弱精症的诊断和治疗具有重要意义。

中文关键词： TDRG1；弱精症；精子功能；信号通路；细胞穿膜肽

英文摘要： Asthenospermia is a common cause for male infertility. It may result from abnormal expression of testis-specific genes. TDRG1 (Testis Development Related Gene 1) is characterized as a primate testis-specific gene identified by our team. Furthermore, our recent findings demonstrated the presence of TDRG1 in the cytoplasm of human normal spermatozoa tail. More importantly, the contents of TDRG1 mRNA and protein were significantly decreased in 60% of the samples from 30 cases of asthenospermia. These results suggest that TDRG1 is involved in the regulation of sperm motility, but its functions and mechanism in the human spermatozoa are required to be elucidated. Thus, this study aims to: 1) systematically characterize the relationship between TDRG1 and asthenospermia under the large scale of clinical samples; 2) comprehensively reveal the functional role of TDRG1 in human spermatozoa using the penetrating peptide TAT carried the TDRG1 recombinant protein or antibody into the samples of asthenospermia or normal spermatozoa on the basis of the fact that the penetrating peptide TAT is able to import foreign proteins into the cytoplasm of human spermatozoa; 3) illustrate the mechanism of TDRG1 in human spermatozoa. This study may shed new lights on functional regulation of human spermatozoa, of which results are important for development of diagnosis and treatment of asthenospermia.

英文关键词： TDRG1;asthenospermia;sperm function;signaling pathway;cell penetrating peptides