Molecular mechanisms regulating human sperm function.

the fertilizing potential of human spermatozoa stems primarily (White and Aitken, 1989; Aitken and Fisher, 1997). During from a need to understand the aetiology of defective sperm the initial stages of capacitation all of these conditions are function, which remains the single, largest, defined cause of reversed. Intracellular calcium concentrations start to rise, ROS human infertility (Hull et al., 1985). Although intracytoplasmic generation is initiated, cAMP concentrations increase and sperm injection (ICSI) has made a major contribution to the spermatozoa develop a highly vigorous form of motility known treatment of the infertile male, the indiscriminant use of this as hyperactivation. Capacitation is also associated with a global technique in the absence of an adequate diagnosis, raises increase in tyrosine phosphorylation, as a consequence of difficulties in terms of the efficient utilization of resources and ROS-induced changes in the redox status of the cells (Aitken the inadvertent transmission of infertility to the offspring. In et al., 1995), and an increase in cAMP generation (Visconti this context it is clear that some severe forms of male infertility et al., 1995b). The induction of tyrosine phosphorylation is do have a genetic origin involving, for example, deletions on one of the most important events in capacitation, since if it is the Y-chromosome (Chandley, 1995). It is also clear that the blocked by tyrosine kinase inhibitors such as genistein, then widely publicized decline in human sperm counts reported in capacitation cannot occur (Aitken et al., 1996a). Knowledge several European countries (Carlsen et al., 1992) is happening of the mechanisms controlling tyrosine phosphorylation during at too fast a rate to be genetic, and probably involves capacitation, and the nature and function of the proteins environmental factors. Male infertility is thus a multifactorial targeted in this process, is therefore central to our understanding phenomenon and elucidation of its many causes is the only of how spermatozoa become primed for fertilization. route to providing rational strategies for the prevention and The importance of redox-regulated reactions in controlling treatment of this condition. the events surrounding capacitation is one of the most significIn order to provide new insights into the causes of male ant insights into sperm cell biology to have emerged in recent infertility, we must first establish a satisfactory model for the years (Bize et al., 1991; Griveau et al., 1994; Aitken et al., cellular mechanisms that drive normal sperm function. In this 1995, 1996a; De Lamirande et al., 1997). However, there are issue of Molecular Human Reproduction we have addressed differences between groups in terms of whether it is superoxide this issue by assembling a series of articles that represent the or hydrogen peroxide which is the major mediator of capacitcurrent state-of-the-art in terms of our understanding of the ation; these are differences of emphasis rather than direction, biochemical mechanisms controlling the functional competence since both of these reactive metabolites are probably involved of human spermatozoa. in controlling different elements of the capacitation process.