Grant: Operating Grant

Infertility is an important human health problem that affects about 16% of couples worldwide; half of these cases can be traced to men. The diagnosis and treatment of this health problem is difficult because many factors are found (but other not yet) as causes. Infertile men often have high levels of reactive oxygen species (ROS) in their semen, molecules normally produced by the cell, but when they are presented in high amounts become toxic. As men age, spermatogenesis is affected resulting in the production of less spermatozoa; these spermatozoa show impaired function. Because of professional and/or work priorities, men are planning to have kids around or after their 40s. Thus, this deliberated delay may impact negatively on their success to achieve fatherhood or could be the cause of transmitting defects to their children. Spermatozoa, as other cell types, can cope with certain levels of ROS by removing them using antioxidants. This proposal is focused on the peroxiredoxin family of antioxidant enzymes and their role in the protection of the male reproductive tract against the toxic effect of high levels of ROS. We recently reported that spermatozoa from infertile men have low levels of peroxiredoxins and we will further elucidate their role in sperm physiology using human spermatozoa as well as animal models. Our PRDX6 knockout model is an attractive tool to study the impact of aging on sperm function. Spermatozoa from these males have significant higher levels of sperm DNA damage and oxidation and lower motility than wild type control. Twelve month-old males have a dramatic reduction of fertility (50% less than the matched age wild type controls). Understanding the role of peroxiredoxins and especially PRDX6 in spermatozoa under physiological conditions will allow us to seek for therapeutic strategies to keep the levels of ROS at the desirable physiological levels in young and aging men seeking fatherhood.