Evaluation of boar sperm as a model system to study the mechanism of spermicidal activity of vanadocenes

bis-Cyclopentadienyl [Cp] complexes of vanadium(IV) or vanadocenes are rapi d and potent inhibitors of human sperm motility with potential as a new cla ss of contraceptive agents. We investigated the utility of boar sperm as a model system to study the mechanisms of drug action because boar sperm lack s phosphocreatine and creatine kinase activity, the essential components of the "phosphagen shuttle" system for human sperm motility, Two representati ve vanadocenes, vanadocene dichloride [VDC] and bis[pentamethylcyclopentadi enyl] vanadium dichloride [VPMDC], in which the bis-Cp rings were substitut ed with five electron-donating methyl groups were evaluated. The concentrat ion-dependent effects of VDC and VPMDC on spermicidal activity, axonemal dy nein adenosine triphosphatase (ATPase) activity, and tyrosine phosphorylati on of global sperm proteins were assessed by computer-assisted sperm analys is, spectrophotometry, and immunoblotting, respectively. Both the unsubstit uted and the pentamethyl-substituted vanadocene induced rapid sperm immobil ization (T-1/2 < 15 s). Substitution of the bis-Cp rings by five methyl gro ups augmented the SIA of VDC threefold. The EC50 values for VDC and VPMDC w ere 2.1 and 0.76 mu M, respectively. Spermicidal activity of vanadocenes wa s not associated with the inhibition of dynein ATPase(s) or increase in tyr osine phosphorylation of sperm proteins. These results suggest that the pot ent spermicidal activity of vanadocenes against boar sperm is mediated by a unique mechanism that is independent of dynein ATPase activity, phosphatas e activity, and phosphocreatine/creatine kinase system. Therefore, boar spe rm is a suitable model for further investigating the molecular mechanism of spermicidal action of vanadocenes. (C) 2000 Academic Press.