Progesterone Induces Hyperpolarization after a Transient Depolarization Phase

Progesterone (P4) induces a membrane depolarization and various ion fluxes (chloride efflux, sodium and calcium influxes), which are required for the human sperm acrosome reaction (AR). By use of the potentiometric fluorescent dye DiSC3(5) and two different technical approaches, the present study aimed to quantify and further analyze P4-induced modifications in mem-brane potential in capacitated human spermatozoa. Spectro-fluorimetric analysis revealed that the mean resting membrane potential of sperm was 258 6 2 mV (n 5 12). When 10 mM P4 was added, the sperm membrane depolarized by;115 mV, partly driven by a Cl2 efflux. It subsequently repolarized to reach a significant lower potential than the initial resting poten-tial in two thirds of the tested samples. The flow cytometry anal-ysis showed a heterogeneous resting membrane potential and revealed that the depolarization-hyperpolarization events con-cerned only subpopulations, between 3 % and 40 % of the sperm cells according to the samples (n 5 7). We hypothesize that P4 has a beneficial effect on the ability of zona pellucida to pro-mote the AR in a sperm subpopulation by increasing the number of hyperpolarized cells presenting a membrane potential that is compatible with the opening of T-type calcium channels by sub-sequent zona pellucida-induced depolarization. acrosome reaction, fertilization, mechanisms of hormone action, progesterone, sper