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Δ9-Tetrahydrocannabinol (Δ9-THC) attenuates mouse sperm motility and male fecundity.
Br J Pharmacol 2012; 165(8):2575-83BJ

Abstract

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(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.

EXPERIMENTAL APPROACH

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 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.

Authors+Show Affiliations

Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, USA. morgandj@indiana.edu

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21615727

Citation

Morgan, Daniel J., et al. "Δ9-Tetrahydrocannabinol (Δ9-THC) Attenuates Mouse Sperm Motility and Male Fecundity." British Journal of Pharmacology, vol. 165, no. 8, 2012, pp. 2575-83.
Morgan DJ, Muller CH, Murataeva NA, et al. Δ9-Tetrahydrocannabinol (Δ9-THC) attenuates mouse sperm motility and male fecundity. Br J Pharmacol. 2012;165(8):2575-83.
Morgan, D. J., Muller, C. H., Murataeva, N. A., Davis, B. J., & Mackie, K. (2012). Δ9-Tetrahydrocannabinol (Δ9-THC) attenuates mouse sperm motility and male fecundity. British Journal of Pharmacology, 165(8), pp. 2575-83. doi:10.1111/j.1476-5381.2011.01506.x.
Morgan DJ, et al. Δ9-Tetrahydrocannabinol (Δ9-THC) Attenuates Mouse Sperm Motility and Male Fecundity. Br J Pharmacol. 2012;165(8):2575-83. PubMed PMID: 21615727.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Δ9-Tetrahydrocannabinol (Δ9-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 - 2011/5/28/entrez PY - 2011/5/28/pubmed PY - 2012/7/28/medline SP - 2575 EP - 83 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 165 IS - 8 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(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. EXPERIMENTAL APPROACH: 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 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/21615727/Δ9_Tetrahydrocannabinol__Δ9_THC__attenuates_mouse_sperm_motility_and_male_fecundity_ L2 - https://doi.org/10.1111/j.1476-5381.2011.01506.x DB - PRIME DP - Unbound Medicine ER -