**1. Introduction**

Male infertility accounts for approximately 40% of all cases of infertility [1] and affects approximately 7% of all men worldwide [2]. Recently, considerable attention has focused on the role of oxidative stress (OS) in the pathophysiology of male infertility. OS is associated with the excessive generation of free radicals, such as reactive oxygen species (ROS), and/or decreased efficacy of antioxidant defenses. In humans, the pervasive impact of OS has been linked to the development of a variety of diseases as diverse as Alzheimer's disease [3], cancer [4], heart failure [5] and obesity [6]. OS is also a prevalent biomarker associated with the semen of approximately 35% of infertile men [7] and the presence of elevated levels of seminal ROS has been reported arising from male reproductive tract pathologies such as varicocele [8], inflammatory [9] and prostate cancer [10]. Owing to their unique architecture, featuring an abundance of oxidizable substrates and limited intracellular antioxidant defenses, the male germ cell is particularly vulnerable to elevated levels of ROS. The resultant OS commonly manifests in a spectrum of adverse sequelae, which drive germ cell dysfunction and culminate in their apoptotic demise [11]. Accordingly, patients with increased ROS levels in their seminal plasma [12] often present with reduced sperm count (oligozoospermia); a condition attributed, at least in part, to apoptosis within the developing germ cell population [13,14]. However, in addition to the loss of sperm viability, OS has also been causally linked to lesions in the motility profile of mature spermatozoa [15].

Progressive sperm movement is required for delivery of the male gamete to the site of fertilization within the ampulla of the Fallopian tubes, as well as the resultant syngamy that facilitates transfer of paternal genetic and epigenetic information to an oocyte during natural conception. Effective sperm motility also plays a crucial role during the assisted reproduction technology (ART) procedures of intrauterine insemination and in vitro fertilization. According to World Health Organization (WHO) criteria [16], the presence of less than 32% of spermatozoa with progressive motility in an ejaculate is defined as asthenozoospermia. It is estimated that asthenozoospermia accounts for as much as 30% of all cases of male infertility [17] and, in the absence of genetic defects, bacterial infection or abnormal semen liquefaction, this condition is often directly linked to the presence of OS in the male reproductive tract and semen [18]. Indeed, elevated levels of seminal ROS have repeatedly been documented in studies of astheno- and oligoasthenozoospermic individuals [18–21]. In terms of the mechanistic basis of sperm dysfunction leading to asthenozoospermia, defective mitochondria and a concomitant reduction in the production of energy required to support normal movement have been identified as a common etiology [18]. However, structural changes in the motility apparatus housed within the sperm flagellum and dysregulation of motility-associated signaling pathways have also been reported in response to OS [22], thus complicating the diagnosis of sperm motility defects. Here, we survey the literature pertaining to the generation of ROS in the male reproductive tract and the deleterious influence of OS on the biochemical pathways and structural features of the sperm cell responsible for modulating their motility. We also highlight the role of antioxidants in combating the burden of OS associated infertility.

### **2. Sources of ROS in Semen**

Seminal ROS originate from a variety of different endogenous and exogenous sources. In addition to generation by spermatozoa themselves, other cellular contaminants such as immature round germ cells, leukocytes and epithelial cells, can also have a direct bearing on the levels of ROS within an ejaculate. Additionally, a number of environmental and lifestyle factors can exert direct and indirect influence over the levels of OS encountered within the male reproductive tract.

### *2.1. Endogenous Sources of ROS*
