CELLULAR COMMUNICATION IN THE EPIDIDYMIS, AN ESSENTIAL COMPONENT OF SPERM MATURATION

间隙连接是相邻细胞之间直接通信的基本结构成分。它们是由相邻细胞之间的孔或连接子排列形成的，从而允许从一个细胞的细胞质到另一个细胞的物质交换。这被称为细胞间隙连接通讯。每个连接子由六种称为连接蛋白（Cx）的蛋白质组成。相邻细胞之间的通讯是协调组织内细胞功能的关键。精子在睾丸中形成。在哺乳动物中，这些睾丸精子不能游泳或受精，这些功能是在精子成熟过程中在附睾获得的。精子成熟的一个关键方面是附睾上皮必须协调附睾的不同区域，以改变精子沐浴和成熟的环境。本研究计划的目的是了解附睾间隙连接通讯的作用和调节，以及它如何调节精子成熟过程。目前的短期目标是通过检查连接蛋白的作用和调节来了解附睾细胞如何分化。为了实现这一目标，我们打算了解雄激素如何调节Cx26基因，该基因仅在青春期前的未分化细胞中表达，此时雄激素水平升高，Cx26被显著抑制。我们打算用这个基因作为模型来理解雄激素如何调节附睾上皮细胞的分化。此外，我们打算使用转基因动物，我们将消除附睾中另一种连接蛋白Cx43的表达，并使用本研究中发现的附睾细胞分化的特定标记物来评估该连接蛋白在主细胞分化中的作用。通过研究附睾细胞通讯和基因表达调控的这些关键基本方面，我们期望对细胞通讯、附睾功能和精子成熟的调控有更好的理解。* * * * * *

Gap junctions are essential structural components for direct communication between neighboring cells. They are formed by the alignment of pores, or connexons, between adjacent cells thereby allowing the exchange of material from the cytoplasm of one cell to another. This is referred to as intercellular gap junctional communication. Each connexon is made up of six proteins that are referred to as connexins (Cx). Communication between neighboring cells is critical for coordinating cellular function within tissues. Spermatozoa are formed in the testis. In mammals, these testicular spermatozoa cannot swim or fertilize, these functions are acquired in the epididymis during sperm maturation. A crucial aspect of sperm maturation is the fact that the epididymal epithelium must coordinate the different regions of epididymis in order to modify the environment in which the sperm bathe and mature. The objectives of this research program are to understand the role and regulation of gap junctional communication in the epididymis and how this regulates the process of sperm maturation. The current short-term objectives are to understand how the cells within the epididymis differentiate by examining the role and regulation of connexins. In order to achieve this we intend to understand how androgens regulate the Cx26 gene, which is expressed only in undifferentiated cells prior to puberty, when androgen levels increase and Cx26 is dramatically repressed. We intend to use this gene as a model to understand how androgens regulate the differentiation of epithelial cells in the epididymis. Furthermore, we intend to use transgenic animals in which we will abolish the expression of another connexin, Cx43, in the epididymis and evaluate the role of this connexin in the differentiation of the principal cells, using specific markers of epididymal cell differentiation identified within this study. By addressing these crucial fundamental aspects of cellular communication and regulation of gene expression in the epididymis, we expect to develop a better understanding of the regulation of cellular communication, epididymal function and sperm maturation. ******