BACKGROUND AND PURPOSE: Numerous studies have shown that N-arachidonoylethanolamine (AEA) can inhibit sperm motility and function but the ability of cannabinoids to inhibit sperm motility is not well understood. We investigated the effects of WIN 55,212-2, a CB 1cannabinoid receptor agonist, and Δ 9-tetrahydracannabinol (Δ 9-THC) on the ATP levels and motility of murine sperm in vitro. In addition, the effects of acute administration of Δ 9-THC on male fecundity were determined. EXPERIMENTAL APPROACH: Effects of D9-THC on basal sperm kinematics were determined using computer-assisted sperm analysis (CASA). Stop-motion imaging was performed to measure sperm beat frequency. The effect of D9-THC on sperm ATP was determined using a luciferase assay. Male fertility was determined by evaluating the size of litters sired by D9-THC-treated males. KEY RESULTS: Pretreatment of sperm for 15 min with 1 μM Δ 9-THC reduced their basal motility and attenuated the ability of bicarbonate to stimulate flagellar beat frequency. Treatment with 5 μM WIN 55,212-2 or 10 μM Δ 9-THC for 30 min reduced sperm ATP levels. In sperm lacking CB 1 receptors this inhibitory effect of WIN 55,212-2 on ATP was attenuated whereas that of Δ 9-THC persisted. Administration of 50 mg·kg -1 Δ 9-THC to male mice just before mating caused a 20% decrease in embryonic litter size. CONCLUSIONS AND IMPLICATIONS: Δ 9-THC inhibits both basal and bicarbonate-stimulated sperm motility in vitro and reduces male fertility in vivo. High concentrations of WIN 55,212-2 or Δ 9-THC inhibit ATP production in sperm; this effect of WIN 55,212-2 is CB 1 receptor-dependent whereas that of Δ 9-THC is not. LINKED ARTICLES: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.
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