ON THE CELLULAR MECHANISMS BY WHICH THE BICARBONATE ION MEDIATES THE EXTRAGENOMIC ACTION OF PROGESTERONE ON HUMAN SPERMATOZOA

Progesterone exerts an extragenomic action on human spermatozoa, induc ing a rapid calcium transient in the acrosomal domain of these cells a nd enhancing their potential for fertilization. This response is known to exhibit an absolute dependence on the presence of extracellular bi carbonate, although the mechanisms underlying this interaction are not understood. In this study, bicarbonate was Found to exert a dose-depe ndent impact on the ability of progesterone to promote sperm-oocyte fu sion in the absence of any collateral effect on sperm motility, The lo ss of sperm function in bicarbonate-free medium was associated with a failure to produce reactive oxygen species, an impaired capacity to ex hibit redox-associated changes in tyrosine phosphorylation, and an app arent incapacity to generate normal calcium transients on exposure to progesterone. These defects were not related to a cAMP deficiency but were associated with a significant fall in intracellular pH. If cytoso lic pH was chemically buffered into the normal range, then the spermat ozoa regained every element of their response to progesterone. These r esults emphasize the importance of an alkaline intracellular milieu fo r the extragenomic action of progesterone an human spermatozoa and str ess the fundamental difference between intracellular and extracellular sources of bicarbonate in maintaining the proton balance within such cells.