Oxidative stress, sperm survival and fertility control

The human spermatozoon is highly susceptible to oxidative stress. This process induces peroxidative damage in the sperm plasma membrane and DNA fragmentation in both the nuclear and mitochondrial genomes. Such stress may arise from a variety of sources including a lack of antioxidant protection, the presence of redox cycling xenobiotics, infiltrating leukocytes and excess reactive oxygen species production by the spermatozoa. Whenever the levels of oxidative stress in the male germ line are high, the peroxidation of unsaturated fatty acids in the sperm plasma membrane ensures that normal fertilization cannot occur. However, at lower levels of oxidative stress, spermatozoa may retain their capacity for fertilization while carrying significant levels of oxidative damage in their DNA. Epidemiological evidence suggests that subsequent aberrant repair of such damage in the zygote may result in the creation of mutations associated with pre-term pregnancy loss and a variety of pathologies in the offspring, including childhood cancer. Thus, while the induction of oxidative stress in spermatozoa is causally involved in the aetiology of male infertility, the prospects of using such a strategy for male contraception is fraught with potential problems, should the suppression of fertility be incomplete and DNA-damaged spermatozoa gain access to the oocyte. (c) 2005 Elsevier Ireland Ltd. All rights reserved.