The CB2 cannabinoid receptor regulates human sperm cell motility

Objective: To analyze the expression and distribution of cannabinoid receptors in human sperm cells and evaluate the effects of activation of receptors by specific agonists and antagonists, with a special emphasis on the CB2 receptor. Design: We performed expression assays for CB1 and CB2 by reverse transcriptase PCR, Western blot, and immunofluorescence techniques in spermatozoa and performed motility analysis after incubation of semen samples with cannabinoid agonists and CB2 antagonist SR144528. Setting: Academic research laboratory. Patient(s): Semen from 50 normozoospermic, healthy human donors. Intervention(s): Spermatozoa isolated from semen by two consecutive swim-ups were used for all techniques. Main Outcome Measure(s): Reverse transcriptase PCR amplification gels, immunoblots, indirect immunofluorescence antibody assays, and percentage of motile sperm. Result(s): We have verified the presence of CB1 and CB2 receptors in human spermatozoa. The distribution of both of these receptors was distinct. Incubation with selective cannabinoid receptor agonists induced a significant reduction in the proportion of rapidly progressive motile spermatozoa, and whereas the CB1 agonist increased the proportion of immobile sperm cells, the CB2 receptor agonist increased the slow/sluggish progressive sperm cell population. The effect of the CB2 agonist was antagonized by the CB2-specific antagonist. Conclusion(s): The functional CB2 cannabinoid receptor is present in human spermatozoa and regulates the sperm motility in a more distinct manner than CB1. (Fertil Steril (R) 2010;93:1378-87. (C)2010 by American Society for Reproductive Medicine.)