Andrology: Modulation of prostaglandin synthesis in mammalian sperm acrosome reaction

Exogenous arachidonic acid induces the acrosome reaction and the production of the prostaglandins PGE<inf>2</inf> and PGF<inf>2α</inf> in bovine spermatozoa. Exogenous PGE<inf>2</inf> also induces the acrosome reaction and PGF<inf>2α</inf> synthesis. To understand better the role of PGE<inf>2</inf> in the induction of PGF<inf>2α</inf> synthesis through modulation of phospholipase A<inf>2</inf>, inhibitors of this enzyme were used. The effects of PGE<inf>2</inf> were blocked by phospholipase A<inf>2</inf> inhibitors and this inhibition was reversed by addition of arachidonic acid. These data indicate that PGE<inf>2</inf> activates phospholipase A<inf>2</inf> to produce arachidonic acid. To determine whether protein kinase C modulates phospholipase A<inf>2</inf> activity in this process, staurosporin, an inhibitor of protein kinase C, was used. The effect of PGE<inf>2</inf> on PGF<inf>2α</inf> production is inhibited by staurosporin and this inhibition was reversed by addition of arachidonic acid indicating that protein kinase C is involved in phospholipase A<inf>2</inf> activation. The effect of exogenous arachidonic acid or PGE<inf>2</inf> on the acrosome reaction is blocked by lipoxygenase inhibitors but not by inhibitors of cyclo-oxygenase, indicating that lipoxygenase products are involved in the mechanism of the acrosome reaction. The presented data shed light on the cross-talk between cyclo-oxygenase and lipoxygenase and their involvement in the sperm acrosome reaction. It is suggested that cyclo-oxygenase products modulate the activity of lipoxygenase which is a key enzyme in the mechanism leading to the acrosome reaction. Stimulation of cyclo-oxygenase to synthesize PGE<inf>2</inf> activates phospholipase A<inf>2</inf> to release arachidonic acid which is the substrate for lipoxygenase activity. Thus, the role of cyclo-oxygenase products is probably to reactivate the phospholipase A<inf>2</inf> which was initially activated via the signal transduction cascade.