Andrology: Modulation of prostaglandin synthesis in mammalian sperm acrosome reaction

Exogenous arachidonic acid induces the acrosome reaction and the production of the prostaglandins PGE₂ and PGF_2α in bovine spermatozoa. Exogenous PGE₂ also induces the acrosome reaction and PGF_2α synthesis. To understand better the role of PGE₂ in the induction of PGF_2α synthesis through modulation of phospholipase A₂, inhibitors of this enzyme were used. The effects of PGE₂ were blocked by phospholipase A₂ inhibitors and this inhibition was reversed by addition of arachidonic acid. These data indicate that PGE₂ activates phospholipase A₂ to produce arachidonic acid. To determine whether protein kinase C modulates phospholipase A₂ activity in this process, staurosporin, an inhibitor of protein kinase C, was used. The effect of PGE₂ on PGF_2α production is inhibited by staurosporin and this inhibition was reversed by addition of arachidonic acid indicating that protein kinase C is involved in phospholipase A₂ activation. The effect of exogenous arachidonic acid or PGE₂ 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 PGE₂ activates phospholipase A₂ to release arachidonic acid which is the substrate for lipoxygenase activity. Thus, the role of cyclo-oxygenase products is probably to reactivate the phospholipase A₂ which was initially activated via the signal transduction cascade.