IFN-gamma alters the human sperm membrane permeability to Ca(2+)

Inflammation in the male genitourinary tract has been associated with the release of pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and elevated reactive oxygen species, which affects spermatozoa capacitation, motility, and the acrosome reaction, along with functions regulated by the concentration of cytoplasmic Ca(2+) ([Ca(2+)]cyto). Though Ca(2+) signaling is of particular significance in sperm, the effect of IFN-γ intracellular calcium on these cells is still unknown. The present study evaluated the effect of IFN-γ on the [Ca(2+)]cyto and Ca(2+) permeability on human sperm. A cell suspension loaded with fura-2 was incubated with or without IFN-γ (from 0 to 2000 pg/ml) for 0, 30, 60, and 120 minutes, and the [Ca(2+)]cyto was measured. The permeability to Ca(2+) was evaluated by the change of the intracellular concentration following an extracellular Ca(2+) pulse. IFN-γ at low concentrations (≤ 500  pg/ml) did not affect the [Ca(2+)]cyto and Ca(2+) permeability of sperm. At a high concentration (2000  pg/ml), IFN-γ did not alter the [Ca(2+)](cyto), but significantly decreased the magnitude and velocity of Ca(2+) entry into the cell. This effect was dependent on incubation time and IFN-γ concentration. This alteration induced by IFN-γ was prevented by the simultaneous incubation of sperm with the antioxidant butylhydroxytoluene (BHT). In conclusion, in vitro, IFN-γ modifies Ca(2+) sperm membrane permeability, probably via lipid peroxidation. IFN-γ in high concentration, as observed in inflammation/infection, can affect [Ca(2+)](cyto) regulation and alter sperm fertilizing capacity.