69 S.J. Parekattil and A. Agarwal (eds.), Antioxidants in Male Infertility: A Guide for Clinicians and Researchers, © Springer Science+Business Media New York 2013 Introduction Mammalian spermatozoa were the first cells reported to produce reactive oxygen species (ROS). The pathophysiological effects of ROS on sperm function have been well studied since the discovery of their toxic effects on sperm motility by McLeod [1]. The study of ROS has since focused on the concept of oxidative stress (OS). Antioxidants scavenge and negate the detrimental effects of ROS, but when over- whelmed because of high ROS or low antioxidant levels, they are unable to control the high degree of ROS-induced damage, resulting in OS [2]. OS can damage proteins, carbohydrates, nucleic acids, and lipids [3, 4]. Spermatozoa are uniquely susceptible to OS because they have limited cell repair systems [5] and antioxidant defenses due to a low cytoplasmic volume. Furthermore, spermatozoa are especially susceptible to lipid peroxidation (LPO) because of the uniquely high content of poly-unsaturated fatty acids (PUFA) present in their plasma membrane. LPO may result in membrane permeabilization, causing an efflux of ATP necessary for flagel- lar movement [6, 7]. OS can further affect sperm function by impairing the viability, motility, and fertilization potential of spermatozoa [8–11]. Conversely, Aitken et al. [12] was the first study to suggest that ROS are involved in normal sperm function. Since, the study of the physiological levels of ROS in sperm function has led to a general acknowledgment that ROS act as intracellular signaling molecules essen- tial to many physiologic processes, including maturation, hyperactivation, capacita- tion, the acrosome reaction (AR), and sperm-oocyte fusion. A better understanding Chapter 4 Physiological Role of Reactive Oxygen Species in Sperm Function: A Review Aaron Thompson, Ashok Agarwal, and Stefan S. du Plessis A. Thompson • A. Agarwal (*) Cleveland Clinic, Center for Reproductive Medicine, Glickman Urological and Kidney Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA e-mail: agarwaa@ccf.org S.S. du Plessis Medical Physiology, Stellenbosch University, Tygerberg, South Africa