Effect of oxidative stress on male reproduction

Abstract

Infertility affects approximately 15% of couples trying to conceive, and a male factor contributes to roughly half of these cases. Oxidative stress (OS) has been identified as one of the many mediators of male infertility by causing sperm dysfunction. OS is a state related to increased cellular damage triggered by oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS). During this process, augmented production of ROS overwhelms the body's antioxidant defenses. While small amounts of ROS are required for normal sperm functioning, disproportionate levels can negatively impact the quality of spermatozoa and impair their overall fertilizing capacity. OS has been identified as an area of great attention because ROS and their metabolites can attack DNA, lipids, and proteins; alter enzymatic systems; produce irreparable alterations; cause cell death; and ultimately, lead to a decline in the semen parameters associated with male infertility. This review highlights the mechanisms of ROS production, the physiological and pathophysiological roles of ROS in relation to the male reproductive system, and recent advances in diagnostic methods; it also explores the benefits of using antioxidants in a clinical setting.

Keywords: Antioxidants; Infertility, male; Oxidative stress; Reactive oxygen species; Spermatozoa.

Fig. 1

Generation of reactive oxygen species. NADPH: nicotinamide adenine dinucleotide phosphate, NADH: nicotinamide adenine dinucleotide, SOD: superoxide dismutase, Cu: copper, Fe: Iron.

Fig. 2

Oxidative stress in male reproduction.

Fig. 3

Measurement of reactive oxygen species (ROS) in sperm suspensions by chemiluminescence assay. (A) Preparation of the samples for ROS measurement. A total of 11 tubes are labeled from S1-S11: Blank, negative control, patient sample, and positive control. Luminol is added to all tubes except blank. Hydrogen peroxide is added only to the positive control. (B) Autolumat 953 plus luminometer used in the measurement of ROS by chemiluminescence assay. Multiple tubes can be loaded simultaneously for measuring ROS. The luminometer is connected to a computer and a monitor, and all the steps can be observed on the screen. (C) A typical graph showing the ROS levels in the 11 tubes (S1-S11). As can be seen, only positive controls have significantly higher levels of ROS. Those producing low levels (Tubes S1-S8) of ROS are seen very close to the X axis. ROS levels measured by the luminometer are expressed as relative light units/s (or RLU/s).