Rebuttal of a role for the epididymis in sperm quality control by phagocytosis of defective sperm.

In a recent Research Article by Sutovsky et al., the authors interpret their results to mean that in the normal animal the epididymis ‘...provides a mechanism for sperm quality control...’ and that ‘ubiquitinated (i.e. defective) sperm are subsequently phagocytosed by the epididymal epithelial cells’ (Sutovsky et al., 2001). This was based on observations that abnormal sperm were ubiquitin-labelled and that the percentage of ubiquitin-labelled sperm decreased from 5% in the caput to 1% in the cauda epididymidis of two animals. This hypothesis is an old one that was discredited over 30 years ago. For it to be valid, two important points need to be established: a loss of sperm in the epididymis and the removal of abnormal spermatozoa by its epithelium. First, the evidence from quantitative testicular histology and cannulation experiments in the normal animal (specifically in the species studied here, the bull) is that the number of sperm leaving the epididymis via the vas deferens is no lower than the number entering it from the testis (Lino et al., 1967; Amann et al., 1974; Amann and Lambiase, 1974), discounting loss during epididymal passage. In this paper, data from only two animals were provided and the potential counting errors of assessing the low percentage of anti-ubiquitin antibody-coated cells found (around 2 percentage points) (World Health Organization, 1999) and the small differences observed render the evidence for a loss of ubiquitinated sperm weak. Second, phagocytosis of sperm by the epididymal epithelial cells does not feature in any of the classical histological and ultrastructural investigations (Nicander, 1957a; Nicander, 1957b; Nicander and Glover, 1973; Hamilton, 1975; Hamilton, 1972) and many others on normal epididymides of many species, including the bull. Given the large number of sperm present in the epididymis at any one time (several billion in the case of the bull, boar and ram), phagocytosis of even 0.1% would be readily detectable on tissue sections examined in the microscope, especially since sperm heads are difficult to digest intracellularly. Reports of sperm within epithelial cells in the normal male tract, mainly in the rete testis efferent ductules and vas deferens-urethral junctions (Cooper and Hamilton, 1977a), amount to very small numbers indeed. The presence of 5-10% dead sperm in the epididymal lumen has been described on numerous occasions at both the light microscopic and ultastructural levels (Cooper and Hamilton, 1977b; NagDas et al., 2000) but no mention is made in these reports of phagocytosis of sperm by epididymal cells. Thirdly, the apparent decrease of labelled cells observed by Sutovsky et al., does not necessarily imply epithelial spermiophagy. Although spermiophagy normally is not seen in the epididymis of all mammals thus far investigated, under certain conditions such as after obstruction or during advanced ageing, spermatozoa can be rarely seen in the cells of the epididymal epithelium. Equally plausible explanations for the observations reported are the welldocumented phenomena of antigen epitope masking by secreted epididymal glycoproteins (Yeung et al., 2000) and the tendency for immature sperm to bind IgG non-specifically (Yeung et al., 1997). We conclude that the paper by Sutovsky et al., presents unconvincing evidence for removal of defective spermatozoa by the normal epididymis and that the data certainly cannot be interpreted as a role for the epididymis in control of sperm quality. Trevor G. Cooper Institute of Reproductive Medicine, University Clinic Münster, Germany