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7 October 2009 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
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Abstract

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.

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, and Vincenzo Di Marzo "A Gradient of 2-Arachidonoylglycerol Regulates Mouse Epididymal Sperm Cell Start-Up," Biology of Reproduction 82(2), 451-458, (7 October 2009). https://doi.org/10.1095/biolreprod.109.079210
Received: 31 May 2009; Accepted: 1 September 2009; Published: 7 October 2009
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KEYWORDS
cannabinoid receptor 1, CB1, CNR1
endocannabinoid
epididymis
sperm maturation
sperm motility and transport
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