Sperm dysfunction is the single most common cause of infertility and affects approximately 1:15 men. Studies using semen assessment as the criteria for sub fertility (sperm concentration <20×106/ ml) show that 1:5 18 year olds are classed as sub-fertile. Thus, male sub-fertility is a very significant global problem and, what is most worrying, is that the recent reports suggesting that its prevalence is increasing. There is an urgent requirement to develop new and robust tests of sperm function to accurately diagnose male infertility and identify what we would call a good sperm. The value of traditional semen parameters (concentration, motility and morphology) in the diagnosis and prognosis of male infertility has been debated for 60 years. Unquestionably, even with appropriate quality assurance, traditional semen parameters can only provide a limited degree of prognostic and diagnostic information for the infertile couple primarily at the lower ranges of the spectrum. It is therefore necessary to develop simple, robust and effective tests of sperm function. Yet, despite the plethora of potential assays available, results have been very disappointing. Even promising initial data for DNA damage of sperm is now questioned. So where do we go? A priority is to develop new tools. Several approaches are being examined from the use of sophisticated microarrays to simplifications of old testing methods. Our approach is to develop new tools concentrating on (1) the sperm proteome (2) calcium mobilisation. Work on the sperm proteome has robustly identified over 2500 proteins and quantitative proteomics (iTRAQ) suggests that a number can be identified as putative candidates of dysfunctional cells. Importantly we are now getting a handle on a plethora of post translational modifications and their functional relevance. Our data on calcium mobilisation and hyperactivation points to the combination of CatSper and store operated channels functioning in calcium regulation during hyperactivation. Currently we are only just documenting the players involved in this critical event but we have shown that a number of men have defective calcium dynamics.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.