Propagation of Per oxidative Damage with Transition Metals

The presence of redox-active metals such as iron and copper in sperm suspensions leads to the breakdown of lipid peroxides to form peroxyl (ROO') and alkoxyl (RO') radicals, according to the following equations:


lipid hydroperoxide + Fe2+ ^ alkoxyl radical + OH- + Fe3+


lipid hydroperoxide + Fe3+ ^ peroxyl radical + H + + Fe2+

In order to stabilize these lipid radicals, abstraction of a hydrogen atom from an adjacent carbon takes place, generating the corresponding acid (ROOH) or alcohol (ROH). Unfortunately, the abstraction of a hydrogen atom from an adjacent lipid creates another carbon-centered radical that combines with molecular oxygen to recreate another lipid peroxide. In order to stabilize, the latter must again abstract a hydrogen atom from a nearby lipid, creating yet another carbon radical, which combines with molecular oxygen to create yet more lipid peroxides. In this manner, a chain reaction is created that, if unchecked, can propagate the peroxidative damage throughout the plasma membrane, leading to a rapid loss of membrane dependent functions. It is because of these catalytic properties that transition metals such as iron and copper are so damaging to sperm function [23, 25, 34].

The ability of transition metals to stimulate lipid peroxidation has been widely used as a diagnostic tool in assessing human sperm quality. Thus, when a ferrous ion promoter (ferrous sulfate and ascorbate) is added to suspensions of human spermatozoa, a sudden increase in lipid peroxide generation is observed [23]. This increase is not due to the de novo first-chain initiation of lipid peroxidation but rather features the catalytic decomposition of preexisting lipid peroxides [35]. It has been proposed that the existence of lipid peroxides in these cells might be due to the ability of chain breaking antioxidants such as vitamin E to impede the propagation of lipid peroxidation cascades initiated during the lifespan of spermatozoa. The resulting accumulation of lipid peroxides can then be induced to decompose during Fe(2+)-promoted lipid peroxidation assays, stimulating lipoperoxidative chain reactions and production of lipid decomposition products such as malondial-dehyde and 4-hydroxyalkenals that can be readily measured [35],

Iron-promoted lipid peroxidation assays therefore provides the andrologist with a picture of the amount of lipid peroxidation the spermatozoa have been exposed to during their lifetime. Such measurements of lipid peroxidation potential in highly purified, leucocyte-free sperm suspensions have revealed the existence of powerful inverse correlations with the motility of the spermatozoa, their viability, their competence for sperm-oocyte fusion and, most significantly, the quality of sperm movement in the original semen samples [36, 37] . Similar negative correlations have been observed between sperm function and ROS generation but, unlike the lipid peroxidation measurements, these relationships were obfuscated by the presence of leucocytes [36]. Measurements of lipid peroxidation levels in the presence of transition metal promoters have therefore secured an important place in the diagnosis of human sperm function [37, 38].

An important aspect of the lipid peroxidation process is that it is very cell-dependent. Thus, a suspension of spermatozoa progressively motile spermatozoa will exhibit very little lipid peroxide formation, whereas dead or moribund cells in the same suspension will be highly loaded with the by-products of this process [38]. Lipid peroxidation may therefore be induced at a relatively late stage in the life history of a sperm cell and only occurs once the antioxidant defense mechanisms have been overwhelmed.

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

Get My Free Ebook

Post a comment