A putative, ubiquitin-dependent mechanism for the recognition and elimination of defective spermatozoa in the mammalian epididymis

The normal structure and function of sperm are prerequisites for successful fertilization and embryonic development, but little is known about how def ective sperm are eliminated during mammalian spermatogenesis. Here, we desc ribe a ubiquitin-dependent, sperm quality control mechanism that resides in the mammalian epididymis, the site of sperm maturation and storage. We use d immunofluorescence, electron microscopy, western blotting and pulse-chase experiments to show that ubiquitin is secreted by the epididymal epitheliu m and binds to the surface of defective sperm. Most of the ubiquitinated sp erm are subsequently phagocytosed by the epididymal epithelial cells. A por tion of defective sperm escapes phagocytosis and can be found in the ejacul ate. Cultured epididymal cells maintain their ability to produce ubiquitin and phagocytose the defective sperm, as well as the ubiquitin-coated micros pheres, in vitro. The surprising phenomenon of cell-surface ubiquitination in defective sperm provides a possible mechanism for sperm quality control in mammals and a new marker of semen abnormalities in men and animals.