New insights into possible causes of male infertility.

Male subfertility/infertility is acknowledged to contribute significantly to infertility problems experienced by couples. In some instances, morphological and/or physiological defects known to interfere with normal sperm function can be identified. However, in others, no obvious cause of fertilization failure can be identified. The recent introduction of molecular methods has made it possible to diagnose more subtle defects that could affect the function of spermatozoa produced by some males. For others, though, the problems may result from defects in the physiological mechanisms that need to be activated in spermatozoa so that they 'switch on' functionally following their release from the male reproductive tract. Capacitation, the term applied to this 'switching on', encompasses a number of changes that, collectively, confer fertilizing potential on sperm cells. This article focuses on two extrinsic factors, one a protein and one a very small peptide, that become associated with spermatozoa either in the epididymis or following contact with seminal plasma. These factors modulate capacitation in vitro in ways that could be very relevant to fertilization in vivo, possibly helping to maximize the fertilizing potential of the few cells that reach the site of fertilization. In some men, defects in either of the factors and the systems they modulate could result in defective fertilization. However, by understanding the underlying mechanisms, it may prove possible to develop new diagnostic techniques and new therapeutic treatments to alleviate the infertility.