Andrologia. 2018;50:e13126. wileyonlinelibrary.com/journal/and | 1 of 13 https://doi.org/10.1111/and.13126 © 2018 Blackwell Verlag GmbH 1 | INTRODUCTION Reactive oxygen species (ROS) production by spermatozoa was initially discovered by MacLeod (1943). Subsequently, Aitken and Clarkson (1987) observed that spermatozoa also produce ROS when exposed to a calcium cascade induced by ionophore A12187. The in‐ flux of calcium and ROS allows capacitation to occur, which is the pro‐ cess by where the spermatozoa’s plasma membrane increases fluidity and gains the ability to fuse with the oocyte (de Lamirande & Gagnon, 1993). By adding catalase, a ROS scavenger, researchers found that the amount of capacitated spermatozoa decreased by 47% (Griveau, Renard, & Lannou, 1994). This proved that ROS play a vital role in sperm maturation and fertilisation capability. Reactive oxygen species can either inhibit or activate several en‐ zymes to facilitate capacitation. The activation of kinases occurs ei‐ ther directly or via a secondary messenger to facilitate the necessary physiological response. These highly reactive, mainly radical‐based oxygen derivatives bind directly to phosphokinase C (PKC) which, in turn, activates PKC and allows it to move to the phosphotyrosine binding domains on the plasma membrane (De Lamirande & O’Flaherty, 2008; Signorelli, Diaz, & Morales, 2012; Visconti et al, 1995). On the other hand, ROS can prevent tyrosine kinase inhibition by oxidising phosphatase, subsequently allowing tyrosine kinases to move to the phosphotyrosine binding domains on the plasma mem‐ brane (Hecht & Zick, 1992). However, the intermediate steps from tyrosine kinase activation to the end of capacitation remain to be fully understood; yet, the end result is an efflux of cholesterol and greater membrane fluidity (Cross, 1998; Davis, 1981) (Figure 1). The plasma membrane of spermatozoa contains extraordinary high amounts of polyunsaturated fatty acids (PUFAs) which con‐ tribute to its membrane fluidity. In turn, these PUFAs render sper‐ matozoa highly susceptible to oxidative damage (Aitken, Harkiss, & Buckingham, 1993). Reactive oxygen species attack of PUFAs generates a cyclic, propagating cycle called a radical chain reaction whereby the unconjugated double‐bond groups of the PUFAs will undergo an initial electrophilic attack by ROS (Aitken, 2017), which will eventually result in the formation of malondialdehyde (MDA), Received: 16 January 2018 | Revised: 8 June 2018 | Accepted: 18 July 2018 DOI: 10.1111/and.13126 INVITED REVIEW Role of oxidative stress, infection and inflammation in male infertility Ashok Agarwal 1 | Mohit Rana 1 | Emily Qiu 1 | Hashem AlBunni 1 | Albert D. Bui 1,2 | Ralf Henkel 1,3 1 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, Ohio 2 Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 3 Department of Medical Biosciences, University of the Western Cape, Bellville, South Africa Correspondence Ashok Agarwal, American Center for Reproductive Medicine, Cleveland Clinic, OH 44195. Email: agarwaa@ccf.org Abstract Oxidative stress (OS), defined as an overabundance of reactive oxygen species (ROS) or a deficiency of antioxidants, has been linked to sperm damage and male infertility. There are many sources of OS and inflammation including varicocele, tobacco usage, alcohol, obesity/metabolic syndrome, leukocytospermia, sexually transmitted dis‐ ease (i.e., Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum), bacterial prostatitis, microorganism mutations leading to more OS, and viral infections (i.e., human immunodeficiency virus, hepatitis). This review is focusing on infection and inflammation‐mediated OS, the inflammatory markers underlying pathology, clinical significance in male infertility, and a brief description of the recommended treatment modalities. KEYWORDS causes of oxidative stress, male genital tract infections, oxidative stress, sexually transmitted diseases