Antioxidant Enzymes and Male Fertility: Lessons from Knockout Models

Significance: Spermatozoa are very sensitive to high levels of reactive oxygen species (ROS) due to the limited antioxidant systems present in these terminal cells. However, tight regulation of ROS levels must be ensured to accomplish the unique goal of the spermatozoon, that is, the transfer of the paternal genome into the mature oocyte during the fertilization process. Thus, it is essential that the restricted antioxidant enzymatic systems are active for sperm function. Recent Advances: Oxidative stress is associated with low sperm quality. High levels of ROS in spermatozoa produce oxidation of lipids, proteins, and DNA that lead to lipid peroxidation, oxidation of essential structural proteins and enzymes, and mutations due to oxidation of DNA. Critical Issues: In this study, we described the available knockout mouse models that helped to better understand the role of different antioxidant enzymes in male fertility. We focused mainly on those studies that directly explore the effects of the lack of these enzymes in male fertility and included information when existing knockout mouse models produced for other purposes were used. Special attention was given in this review to the consequences of the absence of antioxidant enzymes on sperm quality and fertility of aging males from the knockout models. Future Directions: Further studies using novel mouse models lacking different antioxidants and their combinations are essential to understand the consequences of high levels of ROS in aging testes, epididymes, spermatozoa, and embryo development to produce a healthy baby.