Article

Δ9-Tetrahydrocannabinol (Δ9-THC) attenuates mouse sperm motility and male fecundity

Gill Center for Biomolecular Science, Indiana University, Bloomington, IN 47405, USA.
British Journal of Pharmacology (Impact Factor: 4.84). 05/2011; 165(8):2575-83. DOI: 10.1111/j.1476-5381.2011.01506.x
Source: PubMed

ABSTRACT

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.
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.
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.

Download full-text

Full-text

Available from: Charles H Muller
  • Source
    • "Apart from these positive effects, Cannabis has been associated with increased risk of myocardial infarction [7], psychosis [8], impaired locomotor and exploratory behavior [9]. It also negatively affects sperm production [10] and delay in conception in women following smoking of Cannabis sativa [11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of chronic consumption of Cannabis sativa on bleeding time and prothrombin time was studied. Fifteen albino Wistar rats weighing 200-220g were used for the study. They were randomly assigned into 3 groups (control, low dose and high dose), n=5. The control group was administered normal saline (0.1ml/kg) while low dose and high dose groups were administered with 0.1mg/kg and 0.2mg/kg of extracts of Cannabis sativa respectively. Orogastric mode of feeding was used for the three groups, and the feeding lasted for 28 days. All the animals were allowed free access tofeed (normal rat chow) and water. After 28 days, the animals were sacrificed and blood samples were collected for analysis using standard methods. The result showed that the bleeding time and prothrombin time were each significantly (P<0.05) higher in the high dose treated group compared to low dose treated group and control group. Also, the mean platelet count showed that the cannabis sativa treated groups were each significantly higher (P<0.001) compared with the control group. Platelet count in the high dose treated group was significantly higher (P<0.01) compared with the low dose treated group. Cannabis sativa increases bleeding time, prothrombin time and platelet count. Cannabis sativa resulted in a dose dependent increase in bleeding time, prothrombin time and platelet counts. as a result, the indiscriminate use of Cannabis sativa should be discouraged as it could be detrimental to the body's hemostatic mechanisms.
    Full-text · Article · Jul 2015 · International Journal of Science and Research (IJSR)
    • "Apart from these positive effects, Cannabis has been associated with increased risk of myocardial infarction [7], psychosis [8], impaired locomotor and exploratory behavior [9]. It also negatively affects sperm production [10] and delay in conception in women following smoking of Cannabis sativa [11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The effects of chronic consumption of Cannabis sativa on bleeding time and prothrombin time was studied. Fifteen albino Wistar rats weighing 200-220g were used for the study. They were randomly assigned into 3 groups (control, low dose and high dose), n=5. The control group was administered normal saline (0.1ml/kg) while low dose and high dose groups were administered with 0.1mg/kg and 0.2mg/kg of extracts of Cannabis sativa respectively. Orogastric mode of feeding was used for the three groups, and the feeding lasted for 28 days. All the animals were allowed free access tofeed (normal rat chow) and water. After 28 days, the animals were sacrificed and blood samples were collected for analysis using standard methods. The result showed that the bleeding time and prothrombin time were each significantly (P<0.05) higher in the high dose treated group compared to low dose treated group and control group. Also, the mean platelet count showed that the cannabis sativa treated groups were each significantly higher (P<0.001) compared with the control group. Platelet count in the high dose treated group was significantly higher (P<0.01) compared with the low dose treated group. Cannabis sativa increases bleeding time, prothrombin time and platelet count. Cannabis sativa resulted in a dose dependent increase in bleeding time, prothrombin time and platelet counts. as a result, the indiscriminate use of Cannabis sativa should be discouraged as it could be detrimental to the body's hemostatic mechanisms.
    No preview · Article · Jul 2015 · International Journal of Science and Research (IJSR)
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mammalian spermatozoa reach the ability to fertilize only after they complete a complex series of physical-chemical modification, the capacitation. Recently, the endocannabinoid-binding type-1cannabinoid receptor (CB1) and transient receptor potential vanilloid 1 (TRPV1) channel have been proposed to play a key role in the control of capacitation. In particular CB1, acting via a Gi protein/cAMP/PKA pathway, maintains low cAMP levels in early stages of post ejaculatory life of male gametes. By this way it promotes the maintenance of membrane stability, thus avoiding the premature fusion of plasma membrane (PM) and outer acrosome membrane (OAM), which is mandatory for the exocytosis of acrosome content. TRPV1, on the contrary, becomes active during the latest stages of capacitation, and allows the rapid increase in intracellular calcium concentration that leads to the removal of the F-actin network interposed between PM and OAM, leading to their fusion and, ultimately, to the acrosome reaction.
    Full-text · Article · Jan 2012 · Communicative & integrative biology
Show more