The paradoxical effects of pentoxifylline on the binding of spermatozoa to the human zona pellucida.
In the presence of pentoxifylline, human spermatozoa are induced to increase certain motion characteristics; however, the role of this drug in fertilization remains equivocal. In this study, the influence of pentoxifylline on one aspect of fertilization, that is sperm-zona binding, has been examined. Results from a fluorescence label competitive zona binding (CZB) test showed that spermatozoa exposed to a pentoxifylline challenge of between 0.1 and 5 mM, which was curtailed after 1 h by washing, had a decreased (P < 0.01) ability to bind to intact zona compared with control spermatozoa. The washing procedures also removed (decrease P < 0.01 compared with peak values) some of the enhanced motion characteristics induced by pentoxifylline. These results were in contrast with those obtained using experimental conditions that maintained an increased curvilinear velocity (VCL) and lateral head displacement (ALH) (increase P < 0.001 above baseline controls) in the continued presence of pentoxifylline. Using a hemizona binding (HZB) assay, 3 mM pentoxifylline increased (P < 0.001) sperm-zona binding almost 20% above zona binding with unexposed control spermatozoa. It was concluded that, in the presence of pentoxifylline, there is increased sperm binding to the zona pellucida; however, if the drug is removed by washing, the sperm binding to the zona is decreased in concert with the removal of the enhanced motion characteristics. The application of zona solubilization by acidic conditions in a microchamber enabled the precise determination of sperm numbers in both of the sperm-zona binding assays, and the results demonstrated that a wide variation in sperm numbers was observed in each test, with 63-580 spermatozoa bound in the CZB assay and 56-1340 spermatozoa bound on a hemizona.
Paul
M
M
Fertility Laboratory, Hammersmith Hospitals Trust, Queen Charlotte's and Chelsea Hospital, London, UK.
Sumpter
J P
JP
Lindsay
K S
KS
D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D009865:Oocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013081:Sperm Motility / Q000187:drug effects; D013084:Sperm-Ovum Interactions / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*; D015044:Zona Pellucida / Q000187:drug effects / Q000502:physiology*
D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors; D016650:Fluorescein-5-isothiocyanate; D010431:Pentoxifylline