Redox Regulation of Fertility in Aging Male and the Role of Antioxidants: A Savior or Stressor

Oxidative stress (OS), an imbalance between reactive oxygen species (ROS) and antioxidant scavengers, is considered an important underlying mechanism associated with ageing, age-related chronic diseases and reproductive decline in males. However, OS is an important regulator of numerous molecular pathways essential for homeostasis within cells, tissues and systems. A fine balance between factors promoting OS and those that scavenge ROS is critically important. In the male reproductive tract and ejaculate, ROS are critical molecular players in essential reproductive processes, including spermatogenesis, epididymal transport, spermatozoa maturation and post-ejaculation processes such as motility, capacitation and the acrosome reaction. Increasing evidence suggests there is an overlap between age-related OS and male reproductive tract dysfunction correlating with reduced fertility potential due to semen quality decline, endocrine changes and sexual dysfunction. With increasing life expectancy in many regions of the world, together with an increasing paternal age and associated risk of for infertility, pregnancy complications and reduced health potential in the offspring, it is becoming increasingly important to fully understand the mechanism linked with these associations. This review considers the role of ROS and OS in fertility regulation, the ageing process, the role for OS in age-related reproductive decline, the approach to assessment in male infertility and the current use of antioxidants as a therapeutic option. Although evidence suggests exogenous antioxidant supplementation is useful in male infertility, caution to excessive or unnecessary use of these approaches is required to avoid the paradox of antioxidants inhibiting essential and beneficial ROS activities in male reproductive biology.