Environmental Toxicants and Male Reproductive Toxicity: Oxidation-Reduction Potential as a New Marker of Oxidative Stress in Infertile Men

Exposure to various environmental and lifestyle-dependent factors such as heavy and trace metals, hydrocarbons, ethylene glycol ethers, obesity, tobacco, alcohol and recreational drugs etc. have been identified to cause reproductive toxicity in men. A number of toxicants affect spermatogenesis leading to poor semen quality affecting fertility in such men, primarily through the mechanism of oxidative stress. In the male reproductive system, oxidative stress is brought about either by excessive production of extrinsic free radicals or by reduced activity of intrinsic antioxidants thereby disrupting the redox balance. Discrete measures of reactive oxygen species, total antioxidant capacity, and post hoc damage suggest an ambiguous relationship between the redox system and male fertility. Antioxidants work by donating electrons to the oxidants, thereby reducing the chances of oxidants to acquire electrons from other nearby structures and cause oxidative damage. Oxidation-reduction potential (ORP) measures this relationship between oxidants and antioxidants in semen. The MiOXSYS system used to measure ORP requires a small volume (~30 µl) of liquefied semen and the measurement is completed in less than 5 min. The galvanostat-based analyzer uses electrochemical technology to measure the ORP in millivolts (mV) which is then normalized to express as mV/10⁶ sperm/mL. The role of ORP as a surrogate marker to conventional semen quality parameters is a current topic of investigation by a number of researchers and clinicians. It can be measured in semen and seminal plasma up to 2 h of liquefaction. ORP correlates negatively with conventional as well as advanced semen quality parameters, including sperm concentration, total sperm count, total motile sperm count, motility, morphology, and DNA fragmentation thus confirming the association of oxidative stress with male factor infertility. ORP values can differentiate the degree of oxidative stress-induced male infertility. A number of clinical studies involving cohorts of men from USA, Qatar and India have established seminal ORP cut-off values to distinguish fertile men from infertile patients. Monitoring ORP levels may help predict treatment efficacy in patients as higher ORP values are indicative of the progression of infertility. It can also be measured in cryopreserved semen samples, which is important in predicting the success of assisted reproductive techniques (ART). A recent ART study reported higher clinical pregnancy rate in infertile men with low seminal ORP in comparison to patients with high ORP. Findings of recent clinical investigations indicate ORP as a novel, independent and robust diagnostic marker of seminal oxidative stress that should find its place in the male infertility workup algorithm.