REDUCTION OF THE FERTILIZING-CAPACITY OF SEA-URCHIN SPERM BY CANNABINOIDS DERIVED FROM MARIJUANA .1. INHIBITION OF THE ACROSOME REACTION INDUCED BY EGG JELLY

DELTA-9-Tetrahydrocannabinol (THC) and two other major cannabinoids derived from marihuana-cannabidiol (CBD) and cannabinol (CBN)-inhibit fertilization in the sea urchin Strongylocentrotus purpuratus by reducing the fertilizing capacity of sperm (Schuel et al. 1987). Sperm fertility depends on their motility and on their ability to undergo the acrosome reaction upon encountering the egg's jelly coat. Pretreatment of S. purpuratus sperm with THC prevents triggering of the acrosome reaction by solubilized egg jelly in a dose (0.1-100-mu-M) and time (0-5 min)-dependent manner. Induction of the acrosome reaction is inhibited in 88.9 +/- 2.3% of sperm pretreated with 100-mu-M THC for 5 min, while motility of THC-treated sperm is not reduced compared to solvent (vehicle) and seawater-treated controls. The acrosome reaction is inhibited 50% by pretreatment with 6.6-mu-M THC for 5 min and with 100-mu-M THC after 20.8 sec. CBN and CBD at comparable concentrations inhibit the acrosome reaction by egg jelly in a manner similar to THC. THC does not inhibit the acrosome reaction artificially induced by ionomycin, which promotes Ca2+ influx and nigericin which promotes K+ efflux. THC partially inhibits (20-30%) the acrosome reaction induced by A23187, which promotes Ca2+ influx, and NH4OH, which raises the internal pH of the sperm. Addition of monensin, which promotes Na+ influx to egg jelly or to A23187, does not overcome the THC inhibition. Inhibition of the egg jelly-induced acrosome reaction by THC produces a corresponding reduction in the fertilizing capacity of the sperm. The adverse effects of THC on the acrosome reaction and sperm fertility are reversible. These findings show that cannabinoids reduce the fertilizing capacity of sea urchin sperm by inhibiting the induction of the acrosome reaction by egg jelly. THC may affect events in the stimulus-secretion coupling mechanism before the opening of ion channels.