New insights into possible factors contributing to male subfertility.

Male subfertility contributes significantly to fertility problems in couples. Although semen analysis may identify abnormalities in sperm numbers, morphology and/or motility that might contribute to subfertility, in other instances the semen parameters may appear to be normal, but the spermatozoa might be dysfunctional. A number of endogenous and exogenous factors have now been identified that can significantly affect sperm function in vitro and it is possible that they may have similar effects in vivo. Some endogenous factors maintain the spermatozoa in a non-fertilizing state, to avoid them 'burning out' and losing fertility before they reach an oocyte, while others stimulate spermatozoa to become fertile and then hold them in a state of readiness to fertilize. Exogenous environmental molecules, referred to as xenobiotics, have been shown to continuously stimulate spermatozoa so that they become fertile quickly, but then 'burn out'. Defects relating to the endogenous molecules could result in spermatozoa either never becoming fertile or becoming fertile too quickly and so losing fertilizing potential. By understanding the mechanisms involved in promoting sperm fertilizing ability, it may be possible to develop new therapeutic treatments to overcome such defects. (Reprod Med Biol 2005; 4: 45-53).