*Review* **The Importance of Oxidative Stress in Determining the Functionality of Mammalian Spermatozoa: A Two-Edged Sword**

### **Robert J. Aitken 1,2,\* and Joel R. Drevet 3**


3 GReD Institute, INSERM U1103—CNRS UMR6293—Université Clermont Auvergne, Faculty of Medicine, CRBCbuilding,28placeHenriDunant,63001Clermont-Ferrand,France;joel.drevet@uca.fr

**\*** Correspondence: john.aitken@newcastle.edu.au

Received: 3 January 2020; Accepted: 21 January 2020; Published: 27 January 2020

**Abstract:** This article addresses the importance of oxidative processes in both the generation of functional gametes and the aetiology of defective sperm function. Functionally, sperm capacitation is recognized as a redox-regulated process, wherein a low level of reactive oxygen species (ROS) generation is intimately involved in driving such events as the stimulation of tyrosine phosphorylation, the facilitation of cholesterol efflux and the promotion of cAMP generation. However, the continuous generation of ROS ultimately creates problems for spermatozoa because their unique physical architecture and unusual biochemical composition means that they are vulnerable to oxidative stress. As a consequence, they are heavily dependent on the antioxidant protection afforded by the fluids in the male and female reproductive tracts and, during the precarious process of insemination, seminal plasma. If this antioxidant protection should be compromised for any reason, then the spermatozoa experience pathological oxidative damage. In addition, situations may prevail that cause the spermatozoa to become exposed to high levels of ROS emanating either from other cells in the immediate vicinity (particularly neutrophils) or from the spermatozoa themselves. The environmental and lifestyle factors that promote ROS generation by the spermatozoa are reviewed in this article, as are the techniques that might be used in a diagnostic context to identify patients whose reproductive capacity is under oxidative threat. Understanding the strengths and weaknesses of ROS-monitoring methodologies is critical if we are to effectively identify those patients for whom treatment with antioxidants might be considered a rational managemen<sup>t</sup> strategy.

**Keywords:** male infertility; oxidative stress; lipid peroxidation; sperm biology
