Antioxidants and reactive oxygen species in human fertility

The cellular components of the human reproductive system are as vulnerable as other cells to the potential detrimental effects of reactive oxygen species (ROS). Antioxidant protection is thus required, though not yet fully characterized, at sites of gametogenesis, fertilization and implantation. Spermatozoa are highly susceptible to oxidative damage due to the high content of polyunsaturated fatty acids within their plasma membrane and such damage may underlie certain aspects of male infertility. However, oral antioxidant therapy with, for example, Vitamin E or glutathione has to date only achieved limited success in treatment programmes. Infertility treatments involve in vitro manipulation of gametes and embryos, ranging from simple spermatozoa preparation techniques to several days culture, exposing cells to increased oxygen levels and potential oxidative stress compared with in vivo. A considerable body of data has demonstrated the benefits for animal embryo culture and human sperm preparation of antioxidant supplementation as well as the removal of sources of ROS such as leucocytes, although data supporting supplementation for human embryo culture are limited. However, the use of exogenous superoxide dismutase may improve embryo development to the blastocyst stage. Evidence is accumulating for a role for ROS in signalling events mediating both sperm capacitation and luteal function. Potential also exists for ROS (including nitric oxide) to fulfill as yet unidentified roles in modulation signalling, gene expression and/or apoptotic events during fertilization, embryo development and implantation. Increasing knowledge of the mechanisms whereby ROS and endogenous antioxidant systems influence reproductive processes can assist to optimise the application of exogenous antioxidants to fertility treatment.