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Role of Major Endocannabinoid-Binding Receptors during Mouse Oocyte Maturation

Department of Life, Health and Environmental Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Faculty of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy
European Center for Brain Research, Santa Lucia Foundation IRCCS, 00142 Rome, Italy
Department of Medicine, Campus Bio-Medico University of Rome, 00128 Rome, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(12), 2866;
Received: 21 May 2019 / Revised: 6 June 2019 / Accepted: 8 June 2019 / Published: 12 June 2019
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Endocannabinoids are key-players of female fertility and potential biomarkers of reproductive dysfunctions. Here, we investigated localization and expression of cannabinoid receptor type-1 and -2 (CB1R and CB2R), G-protein coupled receptor 55 (GPR55), and transient receptor potential vanilloid type 1 channel (TRPV1) in mouse oocytes collected at different stages of in vivo meiotic maturation (germinal vesicle, GV; metaphase I, MI; metaphase II, MII) through qPCR, confocal imaging, and western blot. Despite the significant decrease in CB1R, CB2R, and GPR55 mRNAs occurring from GV to MII, CB2R and GPR55 protein contents increased during the same period. At GV, only CB1R was localized in oolemma, but it completely disappeared at MI. TRPV1 was always undetectable. When oocytes were in vitro matured with CB1R and CB2R but not GPR55 antagonists, a significant delay of GV breakdown occurred, sustained by elevated intraoocyte cAMP concentration. Although CBRs antagonists did not affect polar body I emission or chromosome alignment, GPR55 antagonist impaired in ~75% of oocytes the formation of normal-sized MI and MII spindles. These findings open a new avenue to interrogate oocyte pathophysiology and offer potentially new targets for the therapy of reproductive alterations. View Full-Text
Keywords: endocannabinoids; receptors; signal transduction; meiosis; oocyte endocannabinoids; receptors; signal transduction; meiosis; oocyte

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Cecconi, S.; Rossi, G.; Oddi, S.; Di Nisio, V.; Maccarrone, M. Role of Major Endocannabinoid-Binding Receptors during Mouse Oocyte Maturation. Int. J. Mol. Sci. 2019, 20, 2866.

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