Abstract
Throughout embryonic and early postnatal development, the mammalian epididymis changes from a straight tube to a highly coiled, complex duct that links the efferent ducts to the vas deferens. Overwhelming evidence points to the importance of this tissue in transforming spermatozoa, which leave the testis as immotile cells without the ability to fertilize oocytes, into fully mature cells that have both the ability to swim and to recognize and fertilize eggs. Under normal conditions and in most mammalian species, the acquisition of these functions is essentially completed by the time sperm enter the proximal cauda epididymis. In addition to sperm maturation, the epididymis also plays an important role in sperm transport, concentration, protection, and storage. A highly specialized and region-specific microenvironment is created along the epididymal lumen by active secretion and absorption of water, ions, organic solutes and proteins as well as by the blood-epididymis barrier. The primary factor regulating epididymal function is androgens, but there is mounting evidence that estrogens, retinoids, and other factors—both from the peripheral circulation and coming directly into the epididymis from the testis via the efferent ducts—play specific regulatory roles. Several epithelial cell types, each showing selective expression of genes and proteins, are differentially distributed along the duct; each cell type shows highly regionalized expression of a wide array of markers. Both epididymal epithelial cells and spermatozoa in the lumen are targets for xenobiotics; such exposures can result in undesirable toxic effects or may provide the basis for the development of novel male contraceptive agents. During aging, both the epididymal epithelium and the germ cells in the lumen undergo a series of dramatic changes. The explosion of knowledge we are witnessing regarding all aspects of epididymal structure and function is laying the basis for a new fundamental understanding of epididymal cell biology and novel therapeutic approaches targeted at this organ.
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