Effect of two complex platinum salts on human sperm motility and acrosome reaction

Hydrogen H2PtCl6, has been shown to induce the human sperm acrosome reactio n in vitro. However, the molecular mechanism underlying this exocytic proce ss has not been studied. Therefore, two structurally and chemically differe nt platinum (Pt) compounds, the potent sensitizer sodium-hexachloro-platina te-(IV), Na-2[PtCl6], and the nonimmunogenic tetraamineplatinum-(II)-chlori de, [Pt(NH3)(4)]Cl-2, were selected for the experiments. Their effects on h uman sperm function and second messenger pathways were investigated. Washed human spermatozoa were treated with different concentrations of both Pt sa lts (0.5-1000 mu M) during or after capacitation for 3 h at 37 degrees C. I n addition, spermatozoa were incubated with Pt salts in calcium-free medium or in the presence of the protein kinase A + C inhibitor H7. Sperm motilit y was evaluated by computer-assisted sperm analysis acrosomal loss was dete cted by triple staining. Compared with the controls (6.6 +/-. 2.4%), the pe rcentages of living acrosome-reacted spermatozoa showed a significant dose- dependent increase (P<0.001) after 3h of incubation with Na-2[PtCl6] (7.9 /- 4.2% for 0.5 mu M to 25.0 +/- 2.9% for 1 mM) and [Pt(NH3)(4)]Cl-2 (7.9 /- 3.9% to 21.0 +/- 5.8%). Sperm motility was markedly reduced in samples c ontaining the highest concentrations of the Pt salts. The acrosome reaction was also significantly increased when spermatozoa had first been capacitat ed and then treated with both Pt salts. Calcium-free medium had no effect o n the ability of both Pt salts to induce the acrosome reaction. However, in cubation of Na-2[PtCl6] in the presence of H7 tendentiously decreased the p ercentage of acrosome-reacted spermatozoa. In conclusion? complex Pt salts such as Na-2[PtCl6] or [Pt(NH3)(4)]Cl-2 influence human sperm functions by inducing the acrosome reaction during or after capacitation. This stimulato ry effect is independent of calcium and seems to be dependent on protein ki nase A or C.