TY - JOUR
T1 - Δ 9-tetrahydrocannabinol (Δ 9-THC) attenuates mouse sperm motility and male fecundity
AU - Morgan, Daniel J.
AU - Muller, Charles H.
AU - Murataeva, Natalia A.
AU - Davis, Brian J.
AU - Mackie, Ken
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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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U2 - 10.1111/j.1476-5381.2011.01506.x
DO - 10.1111/j.1476-5381.2011.01506.x
M3 - Article
C2 - 21615727
AN - SCOPUS:84859027621
SN - 0007-1188
VL - 165
SP - 2575
EP - 2583
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 8
ER -