RANTES与附睾精子的结合机制及对精子运动的影响

精子发育异常是导致男性不育的重要原因，睾丸产生的精子经附睾分泌蛋白的修饰作用才能最终获得动力并成熟。近年来的研究表明RANTES在免疫性不育患者精液中的浓度偏低，但具体作用机制不明。RANTES一般通过与其受体或GAG结合两条途径发挥生物学效应。我们的前期工作证实，附睾分泌的RANTES能与精子结合，但不是通过受体途径，提示RANTES可能通过GAG与精子结合。本项目拟运用形态学和分子生物学手段，在小鼠附睾精子上找到与RANTES共定位的GAG，并证实RANTES与GAG在附睾精子上的结合关系；在此基础上破坏或封闭GAG位点进一步探讨RANTES通过GAG与精子的结合机制；再在整体动物水平上分析RANTES结合量与精子动力之间的关系，并通过构建小鼠附睾RANTES的RNA干扰模型，研究RANTES对精子运动的影响。该项目对进一步阐明精子成熟的调控机制和男性不育的诊断治疗有重要意义。

Sperm abnormalities is the significant reason for male infertility, the sperm which produced by testis would acquire motility and maturity through modification by epididymal protein. Recent studies have demonstrated RANTES in the seminal plasma of immune-infertile men was in significantly lower concentrations, but the detail mechanisms is unknown. RANTES can be gained through interacting with its chemokine receptor(s) or binding to certain glycosaminoglycan (GAGs) subpopulations. Our previous study has demonstrated that RANTES that originating from the epididymis can associate with sperm, but the association was not mediated by its receptors. So, it infered that RANTES may bind to the sperm through interaction with GAG. In this application, we study to apply the techniques of morphology and molecular biology to find the co-localization of RANTES and GAG, make sure that RANTES interaction with sperm mediated by GAG. To explore the binding mechanism of RANTES and GAG by destruction and closed the GAG site. Then research the effect of RANTES on sperm motility in vivo and by construction RNA interference model of RANTES in mouse epididymis. The application will be great significance to further clarify the regulatory mechanism and male infertility diagnosis and treatment.