Antioxidant Paradox in Male Infertility: ‘A Blind Eye’ on Inflammation

Abstract

The pathophysiology of male infertility involves various interlinked endogenous pathways. About 50% of the cases of infertility in men are idiopathic, and oxidative stress (OS) reportedly serves as a central mechanism in impairing male fertility parameters. The endogenous antioxidant system operates to conserve the seminal redox homeostasis required for normal male reproduction. OS strikes when a generation of seminal reactive oxygen species (ROS) overwhelms endogenous antioxidant capacity. Thus, antioxidant treatment finds remarkable relevance in the case of idiopathic male infertility or subfertility. However, due to lack of proper detection of OS in male infertility, use of antioxidant(s) in some cases may be arbitrary or lead to overuse and induction of ‘reductive stress’. Moreover, inflammation is closely linked to OS and may establish a vicious loop that is capable of disruption to male reproductive tissues. The result is exaggeration of cellular damage and disruption of male reproductive tissues. Therefore, limitations of antioxidant therapy in treating male infertility are the failure in the selection of specific treatments targeting inflammation and OS simultaneously, two of the core mechanisms of male infertility. The present review aims to elucidate the antioxidant paradox in male infertility treatment, from the viewpoints of both induction of reductive stress as well as overlooking the inflammatory consequences.

High-Risk HPV with Multiple Infections Promotes CYP2E1, Lipoperoxidation and Pro-Inflammatory Cytokines in Semen of Asymptomatic Infertile Men

“…Moreover, inflammation and OS are closely linked pathologies and establish a vicious loop impairing male fertility [ 7 , 8 , 42 ], including HPV [ 5 ]. The cytokines and chemokines play important roles in fertility and infertility [ 43 ].…”

“…Furthermore, multiple infections, all with HR-HPV genotypes, even induce IL-8 and other metabolic cytotoxic by-products that trigger higher LPO than the SI-HPV group, so there is more cytotoxic damage, which results in a high expression of CYP2E1, affecting the total and enzymatic antioxidant capacity. This effect is caused by the overproduction of free radicals (ROS and RNS) by inflammatory cells (which are among the major sources of ROS/RNS) at the location of the inflammation, thus disrupting cellular functions and leading to a variety of pathologies, including male infertility [ 7 ].…”

“…Male infertility is considered multifactorial with various causes, including sexually transmitted infections (STI) such as human papillomavirus (HPV) [ 1 , 2 , 3 , 4 ] and Chlamydia trachomatis [ 5 , 6 ], as well as chronic inflammation [ 7 ] and oxidative stress (OS) [ 7 , 8 ]. However, the mechanisms associated with these changes in infertile men have not yet been fully described.…”

The Effect of Alpha Lipoic Acid (ALA) Supplementation on the in Vitro Maturation Media of Goat Oocyte on Tumor Alpha Necrosis Factor (TNF-α) Expression and Malondialdehyde (MDA) Levels

“…Oxidative stress can also be induced by the release of reactive oxygen species (ROS) from inflammatory cells 34 . Inflammatory cell-derived ROS have been reported to upregulate the TNF-TNFR inflammatory pathway 35 and activate intracellular signaling cascades to increase proinflammatory gene expression 36,37 .…”

Age-Related Decline of Male Fertility: Mitochondrial Dysfunction and the Antioxidant Interventions

“…Zn, acting as a heavy metal detox, an antibacterial agent, and a hormone balancer, plays key roles in regulating sexual health and functions [ 88 ]. Zn is also an important antioxidant and can improve multiple sperm parameters [ 89 ]. The concentration of zinc in seminal fluid is approximately 30 times higher than in blood.…”