The human spermatozoon--not waving but drowning.
The poor quality of the human ejaculate sets man apart from all other mammalian species. Even in normal fertile men the ejaculate may contain up to 85% abnormal forms according to the World Heath Organization (1999). In the wake of this poor semen quality comes extremely poor fertility (Hull et al, 1985) and the highest rates of aneuploidy, pregnancy loss and birth defects in viviparous vertebrates. Thus, the poor quality of human spermatozoa is reflected in both their capacity for fertilization and their genetic integrity. The ultimate cause of defective sperm function is unknown. In certain patients a genetic basis for male infertility has been identified involving DNA deletions on the long arm of the Y chromosome. Such deletions might explain the impoverished semen quality seen in about 10-14% of men with severely impaired spermatogenesis, but fail to explain the infertility seen in most (>85%) cases of male infertility. One of the key attributes and probable causes of defective sperm function is oxidative stress created by excessive ROS generation by the spermatozoa and/or the disruption of antioxidant defence systems in the male reproductive tract. Excess free radical generation frequently involves an error in spermiogenesis resulting in the release of spermatozoa from the germinal epithelium exhibiting abnormally high levels of cytoplasmic retention. The excess cytoplasm contains enzymes that fuel the generation of ROS by the spermatozoa's plasma membrane redox systems. The consequences of such oxidative stress include a loss of motility and fertilizing potential and the induction of DNA damage in the sperm nucleus. The loss of sperm function is due to the peroxidation of unsaturated fatty acids in the sperm plasma membrane as a consequence of which the latter loses its fluidity and the cells lose their function. The causes and consequences of oxidative damage to the DNA in the sperm nucleus are still not known with certainty. The available evidence suggests that early pregnancy loss and morbidity in the offspring, including childhood cancer, are associated with such damage. Developing animal models with which to establish the validity of these relationships and identifying the environmental factors associated with the proposed 'testicular dysgenesis syndrome' will clearly be important tasks for the future.
Aitken
R John
RJ
Discipline of Biological Sciences, Centre for Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia. jaitken@mail.newcastle.edu.au
Sawyer
Dennis
D
D000014:Abnormalities, Drug-Induced; D000818:Animals; D004249:DNA Damage; D005260:Female; D005306:Fertilization; D006801:Humans; D007248:Infertility, Male / Q000209:etiology; D008297:Male; D008954:Models, Biological; D009154:Mutation; D018812:Paternal Exposure; D011247:Pregnancy; D012661:Semen; D013081:Sperm Motility; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology*; D013736:Testicular Neoplasms / Q000453:epidemiology