A gradient of 2-arachidonoylglycerol regulates mouse epididymal sperm cell start-up.

Gilda Cobellis*, Giulia Ricci, Giovanna Cacciola, Pierangelo Orlando, Stefania Petrosino, Maria Grazia Cascio, Tiziana Bisogno, Luciano De Petrocellis, Teresa Chioccarelli, Lucia Altucci, Silvia Fasano, Rosaria Meccariello, Riccardo Pierantoni, Catherine Ledent, Vincenzo Di Marzo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)


During transit through the epididymis, spermatozoa are normally kept immotile and do not attain the ability to become motile until they reach the caudal epididymis. This study was undertaken to determine whether endocannabinoids play a role in the epididymis and in particular in suppressing the ability of spermatozoa to become motile. We show that the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are high in mouse spermatozoa isolated from the caput (head) of the epididymis, where these cells do not move (or possess sluggish and irregular motility) and decrease dramatically in spermatozoa isolated from the cauda (tail). The subsequent gradient regulates, via autocrine communication, the activity of cannabinoid receptor CNR1 (previously known as CB1) present on the sperm cell membrane and induces caudal spermatozoa to acquire the potential to become motile ("start-up"). Accordingly, the genetic or pharmacological inactivation of CNR1 increases number of motile spermatozoa in caput. Also, blockers of endocannabinoid cellular uptake inhibit the potential to move of spermatozoa and destroy the 2-AG gradient throughout the epididymis. This gradient-regulated mechanism may encourage further research for future therapies related to male infertility.

Original languageEnglish
Pages (from-to)451-458
Number of pages8
Issue number2
Publication statusPublished - 1 Feb 2010


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