New insights into sperm physiology and pathology.
Infertility is a relatively common condition affecting approximately one in ten of the population. In half of these cases, a male factor is involved, making defective sperm function the largest single, defined cause of human infertility. Among other factors, recent data suggest that oxidative stress plays a major role in the etiology of this condition. Spermatozoa spontaneously produce a variety of reactive oxygen species (ROS) including the superoxide anion, hydrogen peroxide and nitric oxide. Produced in small amounts, ROS are functionally important in driving the tyrosine phosphorylation cascades associated with sperm capacitation. However, when ROS production exceeds the spermatozoa's limited antioxidant defenses, a state of oxidative stress is induced characterized by peroxidative damage to the sperm plasma membrane and DNA strand breakage in the sperm nucleus. Such oxidative stress not only disrupts the fertilizing potential of human spermatozoa but also the ability of these cells to create a normal healthy embryo. As a result, DNA damage in human spermatozoa is correlated with an increased incidence of miscarriage and various kinds of morbidity in the offspring. These insights into the pathophysiology of defective sperm function have clear implications for the diagnosis and treatment of male infertility, particularly with respect to the potential importance of antioxidant therapy. These concepts may also be relevant to the design of novel approaches to male contraception that attempt to replicate the pathological situation.
Aitken
R John
RJ
ARC Centre of Excellence in Biotechnology and Development, Hunter Medical Research Institute, Discipline of Biological Sciences, University of Newcastle, Callaghan, NSW, 2308, Australia. John.Aitken@newcastle.edu.au
Baker
Mark A
MA
De Iuliis
Geoffry N
GN
Nixon
Brett
B
D000818:Animals; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D006801:Humans; D007248:Infertility, Male / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013075:Sperm Capacitation / Q000502:physiology; D013081:Sperm Motility / Q000502:physiology; D013094:Spermatozoa / Q000473:pathology* / Q000502:physiology*
D003272:Contraceptive Agents, Male; D017382:Reactive Oxygen Species