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.

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

“…In this system, LPO is not initiated through hydroxyl radical generation, but rather through the ferrous ion-catalysed breakdown of pre-existing lipid hydroperoxide in the sperm plasma membrane and the subsequent propagation of the lipid peroxidation chain reaction via alkoxyl radical generation. [50][51][52][53] According to our experiments, the monosialoganglioside GM1 and the disialoganglioside GD1a have no effect on LPO propagation. However, the generation of malondialdehyde as a breakdown product of lipid peroxide decompensation was significantly decreased (P,0.01) in the presence of the disialoganglioside GD1b and the trisialoganglioside GT1b.…”

Mammalian sperm metabolism: oxygen and sugar, friend and foe

“…The spontaneous lipid peroxidation pathways in mammalian sperm have been described in detail by Alvarez and Storey (1995) and Storey (1997). Briefly, the pathways are the following.…”

Effect of ferrous sulphate and ascorbic acid on motility, viability and lipid peroxidation of crossbred cattle bull spermatozoa

“…The combination of Fe 21 and ascorbate has been used to induce oxidative stress/LPO via hydroxyl radical (OH > ) formation and by increasing the levels of thiobarbituric acid-reactive substances (TBARS) such as malondialdehyde (MDA) that originate from the breakdown of lipid peroxides (Aitken et al, 1993). In sperm cells, spontaneous LPO occurs, but at a lower level than that induced by ferrous sulphate and ascorbate (Storey, 1997).…”