Figure 1.

Mechanisms to explain ‘antioxidant paradox’ pertaining to male infertility, both by the induction of reductive stress and the failure to address the interconnected link of oxidative stress (OS) with inflammation. Various endogenous and exogenous factors may induce OS. OS and inflammatory pathways operate in loops, each triggering the other. Antioxidants act to mitigate excess reactive oxygen species (ROS) to minimize the adverse impacts of OS on male reproductive tissues. If overused, antioxidants may shift the redox scale towards the reductive end causing reductive stress rendering insufficient ROS needed for normal physiological functions of the sperms. Moreover, reductive stress also may revert to OS conditions. Finally, the antioxidants fail to curb the inflammatory responses that may again lead to OS and OS-induced male reproductive disruptions. ER = endoplasmic reticulum; MetS = metabolic syndrome; GSH = reduced glutathione; GSSG = oxidized glutathione; ROS = reactive oxygen species; RNS = reactive nitrogen species; GPx = glutathione peroxidase; Nrf2 = nuclear factor-erythroid factor-2-related factor-2; E2 = estradiol; NFkB = nuclear factor kappa B; MAPK = mitogen activating factor kinase; NO = nitric oxide; PG = prostaglandin.