title: Reactive oxygen species and sperm function--in sickness and in health.
abstract: The ability of spermatozoa to generate reactive oxygen species (ROS) has  been appreciated since the 1940s. It is a universal property of mature  spermatozoa from all mammalian species and a major contributor to the  oxidative stress responsible for defective sperm function. The mechanisms by  which oxidative stress limits the functional competence of mammalian  spermatozoa involve the peroxidation of lipids, the induction of oxidative DNA  damage, and the formation of protein adducts. ROS production in these cells  involves electron leakage from the sperm mitochondria, triggered by a  multitude of factors that impede electron flow along the electron transport  chain. The net result of mitochondrial ROS generation is to damage these  organelles and initiate an intrinsic apoptotic cascade, as a consequence of  which spermatozoa lose their motility, DNA integrity, and vitality. This  pathway of programmed senescence also results in the exteriorization of  phosphatidylserine, which may facilitate the silent phagocytosis of these  cells in the aftermath of insemination, in turn influencing the female tract  immune response to sperm antigens and future fertility. Despite the  vulnerability of sperm to oxidative stress, it is also clear that normal sperm  function depends on low levels of ROS generation in order to promote the  signal transduction pathways associated with capacitation. Modulators of ROS  generation by spermatozoa may therefore have clinical utility in regulating  the fertilizing capacity of these cells and preventing the development of  antisperm immunity. Achievement of these objectives will require a systematic  evaluation of pro- and antioxidant strategies in vivo and in vitro.
authors.affiliation: Priority Research Centre for Reproductive Biology, Faculty of Science, University of Newcastle, Callaghan, NSW 2308, Australia. john.aitken@newcastle.edu.au
authors.forename: R John
authors.initials: RJ
authors.lastname: Aitken
authors.forename: Keith T
authors.initials: KT
authors.lastname: Jones
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Robertson
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis; D004249:DNA Damage; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013075:Sperm Capacitation / Q000502:physiology; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species