Biochemistry of the induction and prevention of lipoperoxidative damage in human spermatozoa

Abstract

Lipid peroxidation occurs in human sperm cells with damage to the cell plasma membrane, leading to loss of cytosolic components and hence to cell 'death'. The peroxidation may be induced at high rates in the presence of Fe2+ and ascorbate. It occurs at slower rates under physiological conditions as spontaneous lipid peroxidation, which has the following characteristics. The rate is constant over the time required for complete loss of motility in the cells of the sperm sample; one can thus use the time to complete loss of motility (TLM) as a ready measure of the rate. Loss of motility occurs at a characteristic extent of lipid peroxidation, assayed in terms of production of the peroxidative breakdown product, malonaldehyde (MA), that is independent of peroxidation rate. For human sperm, this extent corresponds to 0.1 nmol MA/10(8) cells. Human spermatozoa possess the anti-lipoperoxidative defence enzymes, superoxide dismutase (SOD) and glutathione peroxidase plus glutathione reductase (GPX/GRD). The SOD activity is highly variable between human sperm samples while the activities of GPX and GRD are rather more constant. The rates of production of superoxide anion, O2-, and hydrogen peroxide, H2O2, from human spermatozoa are variable, but their sum calculated in O2- equivalents as O2- + 2H2O2 is quite constant. The variability arises from the variability in SOD activity: all H2O2 produced is from O2- due to the action of SOD. The essential role of SOD as defence enzyme is inferred from the observation that TLM of a given sperm sample is directly proportional to the SOD activity of that sample. The essential role of GPX/GRD is inferred from the observation that inhibition of GPX, either with mercaptosuccinate or with complete oxidation of intracellular reduced glutathione, results in a 20-fold increase in peroxidation rate. The capacity of the GPX/GRD system appears to be limited by the glucose-6-phosphate dehydrogenase-catalysed rate of production of NADPH, the required reductive substrate for GRD. Human spermatozoa appear to have enough anti-lipoperoxidative defensive capacity for lifetimes long enough for fertilization but still short enough for ready removal from the female reproductive tract in good time. Too low a defence capacity could lead to male infertility.