The Positive Roles for Reactive Oxygen Species in Human Reproduction; Implications for the Therapeutic Application of Antioxidants

While the pathological impact of reactive oxygen species (ROS) in the aetiology of human infertility has received much attention, this review explores the counterproposal that these highly reactive metabolites play a positive role in mediating reproductive success. The physiological importance of ROS in biological systems can be distilled into three main categories of influence: (1) ROS can oxidize thiols to generate either the corresponding sulfenic acid or disulfide bridges. This oxidizing capacity is critical for several reproductive processes, including the cross linking of sperm chromatin during epididymal maturation, formation of the mitochondrial sheath, and the activation of proteolytic zymogens involved in such processes as ovulation, menstruation, implantation, and parturition. Thiol oxidation is also involved in the suppression of phosphatase activity and the resulting promotion of phosphorylation-dependent signal transduction pathways, which are involved in virtually every aspect of reproduction from sperm capacitation to parturition; (2) The destructive properties of ROS are also biologically significant in the defence against genital tract infections and in mediating such processes as autophagy, apoptosis, and ferroptosis, which are fundamental to the reproductive process; (3) Finally, ROS are involved in controlling the redox status of transition metals (particularly iron and copper) in the active site of many enzymes that are of fundamental importance to reproduction. Given the biological importance of ROS to procreation, we should use antioxidants with care in managing both male and female infertility and avoid the induction of reductive stress.