title: Δ9-Tetrahydrocannabinol (Δ9-THC) attenuates mouse sperm motility and male fecundity.
abstract: OBJECTIVE
  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(1) cannabinoid 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.
  
  
  METHODS
  Effects of Δ(9) -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 Δ(9) -THC on sperm ATP was determined using a luciferase assay. Male fertility was determined by evaluating the size of litters sired by Δ(9) -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
  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.
authors: Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, USA. morgandj@indiana.edu
authors: Daniel J
authors: DJ
authors: Morgan
authors: Charles H
authors: CH
authors: Muller
authors: Natalia A
authors: NA
authors: Murataeva
authors: Brian J
authors: BJ
authors: Davis
authors: Ken
authors: K
authors: Mackie
references: Development. 2003 Apr;130(7):1317-26
references: 12588848
references: Science. 1982 Apr 16;216(4543):315-6
references: 6801767
references: J Clin Endocrinol Metab. 2005 Feb;90(2):984-91
references: 15562018
references: J Cell Sci. 2005 Oct 1;118(Pt 19):4393-404
references: 16144868
references: J Clin Invest. 2006 Aug;116(8):2087-90
references: 16886056
references: Biol Reprod. 2010 Feb;82(2):451-8
references: 19812302
references: Endocrinology. 2010 Dec;151(12):5882-92
references: 20962050
references: Dev Biol. 2006 Aug 15;296(2):353-62
references: 16842770
references: Pharmacol Biochem Behav. 1991 Nov;40(3):609-15
references: 1806948
references: Chem Phys Lipids. 2002 Dec 31;121(1-2):211-27
references: 12505702
references: Biol Reprod. 2009 Feb;80(2):235-42
references: 18987328
references: Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20740-5
references: 19074277
references: Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11131-6
references: 19541620
references: Reprod Fertil Dev. 1996;8(4):581-94
references: 8870082
references: Anat Rec (Hoboken). 2010 Feb;293(2):298-309
references: 19938110
references: Endocrinology. 2009 Oct;150(10):4692-700
references: 19608651
references: Dev Cell. 2005 Aug;9(2):249-59
references: 16054031
references: Development. 1995 Apr;121(4):1129-37
references: 7743926
references: Br J Pharmacol. 2011 Nov;164 Suppl 1:S1-324
references: 22040146
references: Mol Reprod Dev. 1993 Dec;36(4):507-16
references: 8305215
references: Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16501-6
references: 15546993
references: Biol Reprod. 2006 Jul;75(1):82-9
references: 16611862
references: Biol Reprod. 2004 Aug;71(2):540-7
references: 15084484
references: Science. 1999 Jan 15;283(5400):401-4
references: 9888857
references: Biol Reprod. 1991 May;44(5):806-13
references: 1907858
references: Mol Pharmacol. 1986 Mar;29(3):307-13
references: 2869405
references: Mol Reprod Dev. 2002 Nov;63(3):376-87
references: 12237954
references: Br J Pharmacol. 2010 Feb;159(4):831-41
references: 20067470
references: Neuropharmacology. 1990 Feb;29(2):161-5
references: 2158635
references: J Biol Chem. 1999 Aug 20;274(34):24131-6
references: 10446185
references: Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7678-82
references: 8052642
references: Res Reprod. 1976 Jul;8(4):chart
references: 1036204
references: Fertil Steril. 2009 Jun;91(6):2471-6
references: 18565513
references: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2993-8
references: 14976244
references: Development. 1995 Apr;121(4):1139-50
references: 7538069
references: Fertil Steril. 2006 Mar;85(3):653-60
references: 16500334
references: Biochem Pharmacol. 1991 Jul 25;42(4):899-904
references: 1651081
references: Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13483-8
references: 15340140
references: J Exp Zool. 1981 Jan;215(1):35-46
references: 6785374
references: Neuropharmacology. 2004;47 Suppl 1:345-58
references: 15464149
references: Biol Reprod. 1986 Mar;34(2):349-56
references: 3082381