Antioxidant intervention against male infertility: time to design novel strategies

Infertility is a highly prevalent condition, affecting 9–20% of couples worldwide. Among the identifiable causes, the male factor stands out in about half of infertile couples, representing a growing problem. Accordingly, there has been a decline in both global fertility rates and sperm counts in recent years. Remarkably, nearly 80% of cases of male infertility (MI) have no clinically identifiable aetiology. Among the mechanisms likely plausible to account for idiopathic cases, oxidative stress (OS) has currently been increasingly recognized as a key factor in MI, through phenomena such as mitochondrial dysfunction, lipid peroxidation, DNA damage and fragmentation and finally, sperm apoptosis. In addition, elevated reactive oxygen species (ROS) levels in semen are associated with worse reproductive outcomes. However, despite an increasing understanding on the role of OS in the pathophysiology of MI, therapeutic interventions based on antioxidants have not yet provided a consistent benefit for MI, and there is currently no clear consensus on the optimal antioxidant constituents or regimen. Therefore, there is currently no applicable antioxidant treatment against this problem. This review presents an approach aimed at designing an antioxidant strategy based on the particular biological properties of sperm and their relationships with OS.