大鼠附睾管腔高浓度钾离子液体微环境的形成机制及生理功能的研究

The ion transport function of epididymal epithelial cells plays an important role in the formation of the microenvironment of epididymal lumen, which provides a suitable microenvironment for sperm maturation and storage. During the migration in epididymis, the concentration of K+ in the luminal fluid gradually increase and finally higher than that in plasma, moreover , the concentration of K+can be as high as 50mM in the caudal epididymal lumen of rat. It is likely that the high concentration of K+ in caudal epididymal luminal liquid is of great significance for sperm maturation and storage in a resting state. However, little research has been focused on the mechanism underlying the formation of high concentration of K+ in epididymal luminal microenvironment. Some previous experimental data of us has shown that hydrogen sulfide can promote the secretion of potassium ions through the epididymal epithelial cells. Based on this, we intend to combine the in vitro electrophysiological methods, holistic animal methods and the traditional reproductive methods to reveal the mechanisms underlying the formation of high potassium microenvironment of the rat epididymal lumen and the role of hydrogen sulfide in the process. Meanwhile,we will explore weather the high concentration of K+ liquid microenvironment could regulate the motility character of sperm and uncover the molecular mechanism. Finally, assess the relationship between the epididymal endogenous hydrogen sulfide generation disorder / defect and the male reproductive ability. The completion of this subject will illuminate the formation mechanism of epididymal high concentration of K+ liquid microenvironment and the molecular mechanism underlying the regulation of sperm motility by high concentration of K+ microenvironment. Overall, the success of this project will systematically reveal the physiological and pathological roles of high concentration of K+, forming basis for developing creative diagnosis and treatment methods for male infertility or screening novel malecontraceptives.

附睾上皮细胞的离子转运功能为精子的成熟和储存提供了一个适宜的液体微环境。随着附睾移行，其管腔液的中K+浓度逐渐升高，附睾尾部管腔液中K+的浓度可高达50mM为血液K+浓度的10倍左右。附睾尾部管腔高K+的液体微环境对于精子成熟具有重要意义。但关于附睾管腔高浓度K+ 液体微环境形成机制的研究甚少。申请人前期的实验数据表明硫化氢能够促进附睾上皮细胞K+的主动分泌，基于此，申请人拟结合电生理研究、整体动物研究以及传统生殖学方法等，揭示附睾管腔高浓度K+微环境形成的调控机制以及硫化氢在其中所发挥的作用，同时探索高浓度K+的液体微环境对于精子运动的调控作用及其分子机制，最后评估附睾内源性硫化氢的生成紊乱/缺陷与雄性不育的关联。本课题的完成将明了附睾管腔高浓度K+液体微环境的形成机制，以及高浓度K+液体微环境对精子运动调控的分子机制，为男性不孕不育疾病的诊疗以及开发新型避孕药物提供新的思路和科学依据。

附睾上皮细胞的离子转运功能为精子的成熟和储存提供了一个适宜的液体微环境。随着附睾移行，其管腔液的中钾离子浓度逐渐升高，附睾尾部管腔液中钾离子的浓度可高达50 mM，为血液钾离子浓度的10倍左右。附睾尾部管腔高钾液体微环境对于精子成熟具有重要意义。但关于附睾管腔高浓度钾离子液体微环境形成机制的研究甚少。在本项目中，申请人结合离体电生理研究、整体动物研究以及传统生殖学方法等，揭示了附睾管腔高浓度钾离子微环境形成的调控机制，深入探究了硫化氢在其中所发挥的作用，同时初步探究了高浓度钾离子液体微环境对于精子运动的调控作用及其分子机制，评估了附睾内源性硫化氢的生成紊乱/缺陷与雄性精子活力降低的关联。