A gradient of 2-arachidonoylglycerol regulates mouse epididymal sperm cell start-up.
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.
Cobellis
Gilda
G
Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Napoli, Italy.
Ricci
Giulia
G
Cacciola
Giovanna
G
Orlando
Pierangelo
P
Petrosino
Stefania
S
Cascio
Maria Grazia
MG
Bisogno
Tiziana
T
De Petrocellis
Luciano
L
Chioccarelli
Teresa
T
Altucci
Lucia
L
Fasano
Silvia
S
Meccariello
Rosaria
R
Pierantoni
Riccardo
R
Ledent
Catherine
C
Di Marzo
Vincenzo
V
D000818:Animals; D001095:Arachidonic Acids / Q000032:analysis* / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000032:analysis / Q000037:antagonists & inhibitors; D063388:Endocannabinoids; D004822:Epididymis / Q000737:chemistry* / Q000166:cytology*; D005989:Glycerides / Q000032:analysis* / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000502:physiology*; D013081:Sperm Motility / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C094503:glyceryl 2-arachidonate