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

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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.