The decline of porcine sperm motility by geldanamycin, a specific inhibitor of heat-shock protein 90 (HSP90)

Sperm motility is an important parameter for fertility. The molecular mecha nisms of mammalian sperm motility are still largely undefined. Our previous observations suggested that heat shock protein 90 (HSP90) may be associate d with porcine sperm motility. The aim of the present study was to further characterize the plausible novel function of HSP90 on sperm motility. Semen from normal, sexually mature boars with sperm motility higher than 80% was used. An HSP90-specific inhibitor, geldanamycin (GA), was added to diluted semen at 0.5, 1.0, 2.5 or 5.0 mu g/mL, and the semen was then incubated at 37 degrees C for 15, 30, 45 or 60 min. Sperm motility was determined by us ing computer-assisted semen analyzer at the end of incubation. The results indicated that GA significantly reduced sperm motility in a dose and time d ependent manner. Moreover, incubation of semen with 5.0 mu g/mL GA for 15 m in completely stopped sperm motility. To test the reversibility of the GA e ffect on sperm motility, GA was removed after 30 min incubation and was rep laced with fresh extender alone or with extender plus 5 mM caffeine, then i ncubated for another 15, 30, 45 or 60 min. The results showed that simply r emoving GA did not reverse the inhibitory effect on sperm motility, while a dding caffeine partially reversed this inhibitory effect. However, the effe ct of 2.5 or 5.0 mu g/mL GA was not reversed by caffeine. Considering the s pecificity of GA targeting to HSP90, the above observations suggested that HSP90 may play a crucial role in regulating porcine sperm motility. (C) 200 0 by Elsevier Science.