Causes and consequences of DNA damage in spermatozoa: importance of oxidative stress in the pathological disruption of mammalian sperm function

Oxidative stress plays a major role in the life of mammalian spermatozoa. These cells are professional generators of reactive oxygen species (ROS), which appear to largely derive from the sperm mitochondria. The oxidative stress created by these organelles appears to play a facilitatory role in driving the physiological changes associated with sperm capacitation. However when generated in excess mitochondrial ROS generation induces high levels of lipid peroxidation, which in turn impairs membrane functions critical for the maintenance of sperm function including the capacity to fertilize the oocyte. Furthermore the lipid aldehydes generated as a consequence of lipid peroxidation bind to proteins in the mitochondrial electron transport chain, including succinate dehydrogenase, and trigger yet more ROS generation in a self-perpetuating cycle. The high levels of oxidative stress created as a result of this process ultimately damage the DNA in the sperm nucleus. Indeed, DNA damage in the male germ line appears to be almost exclusively oxidatively induced, reflecting the limited capacity of these cells to protect themselves against ROS-mediated stress. The consequences of DNA damage in the male germ line include impaired fertilization, disrupted embryonic development, an increased risk of miscarriage and ill health in the offspring. From a domestic animal perspective, such DNA damage is particularly significant because it is likely to have a major impact on the true breeding of traits. In light of the foregoing, the evaluation of antioxidant treatments for the alleviation of oxidative stress in the male germ line is a topic undergoing active consideration.