Heparin and glutathione: physiological decondensing agents of human sperm nuclei

It has been proposed that reduced glutathione (GSH) or other thiol reagents may participate in the basic mechanism by which sperm-decondensing activity is accomplished. However, in vitro, these reagents seem to be inactive and require the presence of other chemicals, usually detergents. Heparin binds specifically to the sperm membrane and provokes the decondensation of human sperm and the activation of DNA transcription and synthesis. However, the concentrations at which these effects occur seem to be higher than those expected under physiological conditions. In the present study, thiol reagents at 10 mM concentration, either alone or combined, were completely ineffective in inducing any significant nuclear decondensation after prolonged exposures (24 hr) of incubation. Heparin, 153.8 microM, was capable of inducing only a small increase in nuclear swelling. However, GSH at concentrations as low as 0.1 mM in combination with heparin induces decondensation of human sperm nuclei in vitro. When GSH concentration was kept constant at 5 mM, nuclear decondensation was induced with heparin at concentrations as low as 11.6 microM, and a maximal decondensation (90%) was obtained with only 21.6 microM of heparin. The latter is more than ten times less than the minimal active concentration of heparin used alone.