title: A gradient of 2-arachidonoylglycerol regulates mouse epididymal sperm cell start-up.
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.
authors.affiliation: Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Gilda
authors.initials: G
authors.lastname: Cobellis
authors.forename: Giulia
authors.initials: G
authors.lastname: Ricci
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cacciola
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Orlando
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cascio
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bisogno
authors.forename: Luciano
authors.initials: L
authors.lastname: De Petrocellis
authors.forename: Teresa
authors.initials: T
authors.lastname: Chioccarelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.forename: Silvia
authors.initials: S
authors.lastname: Fasano
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meccariello
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pierantoni
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: 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
chemical_list: 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