Human spermatozoa: revelations on the road to conception.

Human spermatozoa are highly complex specialized cells designed to survive a long and perilous journey from the site of insemination to the upper reaches of the female reproductive tract where fertilization occurs. During this journey, these cells have to run the gauntlet laid down by the female immune system and time their physiological maturation so that as soon as an egg appears in the Fallopian tube, they are equipped to recognize this cell and participate in a remarkable cascade of cellular interactions culminating in fertilization. Despite their high level of specialization, human spermatozoa are notoriously inadequate and appear to be major contributors to the poor fertility that characterizes our species. Defective spermatozoa are also known to have a major impact on the progress of pregnancy and the health trajectory of the offspring, resulting in paternally mediated increases in miscarriage rate and a range of diseases in the progeny, including dominant genetic diseases and cancer. The causes of defective sperm function are complex and involve both genetic and environmental impacts, as well as paternal age. Where genetic factors are involved, there is a concern that the widespread use of assisted conception technologies will serve to enhance the retention of poor fertility genes in the population such that the more we use assisted reproductive technologies in one generation the more we shall need them in the next. These observations may have important implications for the health and well-being of children and for the provision of reproductive healthcare services for future generations.