Characterization of the endocannabinoid system in boar spermatozoa and implications for sperm capacitation and acrosome reaction.
Anandamide (AEA) is the endogenous ligand of cannabinoid (CB) receptors, and as such it plays several central and peripheral activities. Regulation of female fertility by AEA has attracted growing interest, yet a role for this endocannabinoid in controlling sperm function and male fertility in mammals has been scarcely investigated. In this study we report unprecedented evidence that boar sperm cells have the biochemical machinery to bind and degrade AEA, i.e. type-1 cannabinoid receptors (CB1R), vanilloid receptors (TRPV1), AEA-synthesizing phospholipase D (NAPE-PLD), AEA transporter (AMT) and AEA hydrolase (FAAH). We also show that the non-hydrolyzable AEA analogue methanandamide reduces sperm capacitation and, as a consequence, inhibits the process of acrosome reaction (AR) triggered by the zona pellucida, according to a cyclic AMP-dependent pathway triggered by CB1R activation. Furthermore, activation of TRPV1 receptors seems to play a role of stabilization of the plasma membranes in capacitated sperm, as demonstrated by the high incidence of spontaneous AR occurring during the cultural period when TRPV1 activity was antagonized by capsazepine. We show that sperm cells have a complete and efficient endocannabinoid system, and that activation of cannabinoid or vanilloid receptors controls, at different time-points, sperm functions required for fertilization. These observations open new perspectives on the understanding and treatment of male fertility problems.
Maccarrone
Mauro
M
Department of Biomedical Sciences, University of Teramo, Pizza A. Moro 45, 64100 Teramo, Italy. mmaccarrone@unite.it
Barboni
Barbara
B
Paradisi
Andrea
A
Bernabò
Nicola
N
Gasperi
Valeria
V
Pistilli
Maria Gabriella
MG
Fezza
Filomena
F
Lucidi
Pia
P
Mattioli
Mauro
M
D020101:Acrosome Reaction / Q000502:physiology*; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D063388:Endocannabinoids; D005260:Female; D008297:Male; D010739:Phospholipase D / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013075:Sperm Capacitation / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*; D013552:Swine; D050916:TRPV Cation Channels / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D000242:Cyclic AMP; D063388:Endocannabinoids; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D050916:TRPV Cation Channels; D000099252:Fatty Acid Amide Hydrolases; C494484:TRPV1 receptor; C078814:anandamide