Reduction of the fertilizing capacity of sea urchin sperm by cannabinoids derived from marihuana. I. 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 microM) and time (0-5 min)-dependent manner. Induction of the acrosome reaction is inhibited in 88.9 +/- 2.3% of sperm pretreated with 100 microM 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 microM THC for 5 min and with 100 microM 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Schuel
H
H
Department of Anatomical Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, SUNY 14214.
Berkery
D
D
Schuel
R
R
Chang
M C
MC
Zimmerman
A M
AM
Zimmerman
S
S
D000177:Acrosome / Q000187:drug effects / Q000502:physiology*; D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002185:Cannabidiol / Q000494:pharmacology*; D002187:Cannabinol / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D005306:Fertilization / Q000187:drug effects*; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008985:Monensin / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D012617:Sea Urchins; D013084:Sperm-Ovum Interactions / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects; D015044:Zona Pellucida / Q000502:physiology
D002185:Cannabidiol; D000001:Calcimycin; D015759:Ionomycin; D000641:Ammonia; D013759:Dronabinol; D002187:Cannabinol; D008985:Monensin; D009550:Nigericin