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

附睾中的细胞通讯，精子成熟的重要组成部分

• 批准号: RGPIN-2016-06432
• 负责人: Cyr, Daniel
• 金额: $ 2.55万
• 依托单位: Institut national de la recherche scientifique
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630975
• 关键词: CELLULAR; COMMUNICATION; EPIDIDYMIS; ESSENTIAL; COMPONENT

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.

间隙连接是相邻细胞之间直接通讯的重要结构成分。它们是通过相邻细胞之间的孔或连接子的排列形成的，从而允许物质从一个细胞的细胞质交换到另一个细胞。这被称为细胞间间隙连接通讯。每个连接子由称为连接蛋白（Cx）的六种蛋白质组成。相邻细胞之间的通信对于协调组织内的细胞功能至关重要。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中获得的。精子成熟的一个重要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。本研究的目的是了解附睾缝隙连接通讯的作用和调节，以及它如何调节精子成熟的过程。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内细胞的分化。为了实现这一目标，我们打算了解如何雄激素调节Cx26基因，这是只在未分化的细胞表达青春期前，当雄激素水平增加，Cx26显着抑制。我们打算用这个基因作为模型来了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，我们将取消另一个连接蛋白，Cx43，在附睾中的表达和评估的作用，这种连接蛋白在主细胞的分化，使用本研究中确定的附睾细胞分化的特异性标志物。通过解决这些至关重要的基本方面的细胞通讯和调控的基因表达在附睾，我们希望开发一个更好地了解细胞通讯，附睾功能和精子成熟的调节。