## 3 Oxidative Stress  
Oxidative stress (OS) refers to an imbalance between the production and accumulation of ROS and the biological system's ability to detoxify these ROS in cells and tissues [26]. These ROS are radical and nonradical oxygen species that form through partial oxygen reduction within the mitochondria [27]. Oxidative stress contributes to multiple pathological conditions and diseases [28]. For example, moderate oxidative stress may cause cell dysfunction and altered behaviour, such as accelerated senescence, abnormal proliferation, dysregulated inflammatory responses and cell tumorigenesis. In contrast, high OS usually causes cell death (e.g., oncosis, apoptosis and autophagy) [29]. Cells have an antioxidant defence system that is made up of enzymes (e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and non-enzymatic molecules (e.g., ascorbic acid,tocopherol, caroten) that can neutralise or scavenge ROS [30]. However, with the abundance of exogenous and endogenous sources of ROS, reproductive cells, in particular, lose the ability to balance the levels of oxidants and antioxidants over time, leading to damage to cellular constituents, such as lipids, DNA and proteins [31; 32], which further complicates the functions of the reproductive cells and lead to male infertility [33]. For instance, OS is a significant cause of sperm cell dysfunction and contributes to the aetiology of male infertility due to the impairment of both spermatozoa's structural and functional integrity [34; 35]. It disrupts the integrity of the DNA because of concurrent damage to proteins and lipids present in the sperm cell plasma membrane, affecting cell membrane fluidity and permeability [36]. The presence of high levels of DNA damage in human spermatozoa has been correlated with adverse clinical outcomes, including recurrent pregnancy loss, dominant genetic disorders and infertility. Oxidative stress affects sperm function in two ways: by damaging the sperm nuclear and mitochondrial DNA (mtDNA), which is associated with shorter telomere length, formation of the oxidative base adduct 8-hydroxy-deoxyguanine (8-OHdG) and fragmentation of mitochondrial DNA; or by damaging the sperm plasma membrane and thus affecting sperm motility and its ability to fuse with the oocyte often leading to genome hypermutability, genetic instability, single-strand and double-strand breaks, aberrant DNA damage, Leydig cell dysfunction and finally leading to infertility (see Figure 1). Furthermore, the risk factors that increase ROS in the male genital tract can create an imbalance in the production of oxidants and the scavenging capacity of antioxidant enzymes, consequently leading to OS, as illustrated in Figure 1. In addition, high levels of ROS may disrupt the hormonal balance that regulates male reproductive functions by acting on the hypothalamic-pituitary-gonadotropic (HPG) axis, thus reducing the secretion of LH and FSH from the anterior pituitary gland [37]. The reduced LH secretion results in failure to stimulate Leydig cells to produce sufficient testosterone [38], while reduced FSH negatively affects the release of androgen-binding protein (ABP), which helps in concentrating testosterone. This causes an overall decrease in Leydig cells' function and, in turn, affects the proteins mediating cholesterol uptake into the mitochondria, such as the steroidogenic acute regulatory (StAR) protein, or by increasing concentrations of inflammatory cytokines [39], and consequently decreasing circulating testosterone [40], which results in unregulated spermatogenesis and suppression of sexual behaviour [7]. In addition, obesity results in the excessive production of ROS by stimulating the adipocyte cells to produce leptin, the critical regulatory adipokine [41].