Role of Oxidative Stress in the Etiology of Sperm DNA Damage

Abstract

DNA damage in human spermatozoa is a source of some concern because of its association with impaired conception, disrupted embryonic development, increased rates of miscarriage, and morbidity in the offspring. Oxidative stress appears to be the single most important cause of sperm DNA damage, although the factors responsible for the creation of this stress are currently unresolved. What appears certain is that there is an extremely close link between DNA damage in spermatozoa and impaired spermiogenesis, leading to poor chromatin remodeling. We propose that the latter is associated with the creation of vulnerable spermatozoa that readily default to an apoptotic pathway characterized by the generation of reactive oxygen species by the mitochondria and the creation of oxidative DNA adducts that subsequently result in strand breakage. The impairment of spermiogenesis may itself be the result of oxidative stress in the testes created by a wide range of clinical and environmental factors including testicular torsion, varicocele, diabetes, lifestyle factors such as smoking, and excess exposure to a range of environmental toxicants. If oxidative stress is at the heart of DNA damage in the germ line, then there should be a place for antioxidant therapy in the amelio-ration of this condition. Carefully controlled trials designed to examine the efficacy of different antioxidant formulations are now urgently needed.