EFFECT OF PENTOXIFYLLINE AND PROGESTERONE ON HUMAN SPERM CAPACITATION AND ACROSOMAL EXOCYTOSIS

The effects of pentoxifylline and progesterone on human sperm capacitation and acrosomal exocytosis were investigated using chlortetracycline (CTC) fluorescence. Continuous exposure to 3.60 mM pentoxifylline caused significant changes in distribution of the three CTC patterns (F, B and AR) compared with control suspensions. Initially, the main effect was promotion of the F to B transition, followed by increases in acrosome-reacted (AR) pattern cells as well. Such responses would be consistent with a pentoxifylline-mediated inhibition of cAMP phosphodiesterase leading to increased availability of cAMP. When continuous and short-term exposure to pentoxifylline were compared, very similar responses were observed: both pentoxifylline-treated groups had significantly more capacitated cells (B and AR patterns) than controls. Progesterone tested at 1, 10 and 100 mu g ml(-1) elicited a similar response to that observed with pentoxifylline, with both capacitation and acrosomal exocytosis being stimulated. Cells incubated in 2xCa(2+) (3.6 mM) medium were even more responsive to progesterone treatment than those in standard 1xCa(2+) (1.8 mM) medium, with a threefold decrease in cells exhibiting the F pattern (characteristic of uncapacitated, acrosome-intact cells) and a marked increase in AR cells. These responses are consistent with a progesterone-mediated rise in intracellular Ca2+ that could promote completion of capacitation and initiation of acrosomal exocytosis. Used in combination, pentoxifylline followed by progesterone treatment produced significantly more AR pattern cells than either compound individually. Given the demonstrated ability of pentoxifylline to promote the F to B transition and hence to increase the proportion of capacitated cells able to respond to progesterone, the observed enhanced response to progesterone is not suprising. These results are consistent,vith previous reports of enhanced fertilizing ability of pentoxifylline-treated suspensions and increased acrosomal exocytosis following progesterone treatment.