Role of reactive oxygen species in male infertility

Urology. 1996 Dec;48(6):835-50. doi: 10.1016/s0090-4295(96)00313-5.


Human spermatozoa exhibit a capacity to generate ROS and initiate peroxidation of the unsaturated fatty acids in the sperm plasma membrane, which plays a key role in the etiology of male infertility. The short half-life and limited diffusion of these molecules is consistent with their physiologic role in key biological events such as acrosome reaction and hyperactivation. The intrinsic reactivity of these metabolites in peroxidative damage induced by ROS, particularly H2O2 and the superoxide anion, has been proposed as a major cause of defective sperm function in cases of male infertility. The number of antioxidants known to attack different stages of peroxidative damage is growing, and it will be of interest to compare alpha-tocopherol and ascorbic acid with these for their therapeutic potential in vitro and in vivo. Both spermatozoa and leukocytes generate ROS, although leukocytes produce much higher levels. The clinical significance of leukocyte presence in semen is controversial. Seminal plasma confers some protection against ROS damage because it contains enzymes that scavenge ROS, such as catalase and superoxide dismutase. A variety of defense mechanisms comprising a number of anti-oxidants can be employed to reduce or overcome oxidative stress caused by excessive ROS. Determination of male infertility etiology is important, as it will help us develop effective therapies to overcome excessive ROS generation. ROS can have both beneficial and detrimental effects on the spermatozoa and the balancing between the amounts of ROS produced and the amounts scavenged at any moment will determine whether a given sperm function will be promoted or jeopardized. Accurate assessment of ROS levels and, subsequently, OS is vital, as this will help clinicians both elucidate the fertility status and identify the subgroups of patients that respond or do not respond to these therapeutic strategies. The overt commercial claims of antioxidant benefits and supplements for fertility purposes must be cautiously looked into, until proper multicentered clinical trials are studied. From the current data it appears that no single adjuvant will be able to enhance the fertilizing capacity of sperm in infertile men, and a combination of the possible strategies that are not toxic at the dosage used would be a feasible approach.

Publication types

  • Review

MeSH terms

  • Antioxidants / therapeutic use
  • Forecasting
  • Glutathione / therapeutic use
  • Humans
  • Infertility, Male / drug therapy
  • Infertility, Male / etiology*
  • Infertility, Male / metabolism*
  • Leukocytes
  • Male
  • Reactive Oxygen Species / metabolism*
  • Semen / cytology
  • Semen / metabolism
  • Specimen Handling
  • Spermatozoa / physiology
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / metabolism
  • Varicocele / complications
  • Varicocele / metabolism


  • Antioxidants
  • Reactive Oxygen Species
  • Glutathione