Type 2 cannabinoid receptor contributes to the physiological regulation of spermatogenesis. Issue 4 (15th December 2015)

• Record Type: Journal Article
• Authors: Di Giacomo, Daniele; De Domenico, Emanuela; Sette, Claudio; Geremia, Raffaele; Grimaldi, Paola
• Is Part Of: FASEB journal. Volume 30:Issue 4(2016)
• Page Start: 1453
• Page End: 1463
• Publication Date: 2015-12-15
• Subjects: endocannabinoid system -- histone methylation -- meiosis -- retinoic acid; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.15-279034
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract : Type 2 cannabinoid receptor (CB2 ) has been proposed to play a pivotal role in meiotic entry of male germ cells, similar to retinoic acid (RA). In this study, we showed that activation of CB2 with the specific agonist JWH133 [3‐(1', 1'‐dimethylbutyl)‐1‐deoxy‐8‐THC] (IC50 10 –6 M) mimics epigenetic events induced by RA (IC50 10 –7 M) in spermatogonia. Both JWH133 and RA treatments stimulate the expression of the meiotic genes c‐ Kit and Stra8, by up‐regulating H3K4me3 and down‐regulating H3K9me2 levels in genomic regions flanking the transcription start site. Moreover, both agents increase the expression of Prdm9, the gene encoding a meiosis‐specific histone, H3K4me3 methyltransferase, which marks hot‐spots of recombination in prophase I, thus resulting in a global increase in H3K4me3. Notably, prolonged administration of JWH133 to immature 7 dpp CD‐1 mice induced an acceleration of the onset of spermatogenesis, whereas the specific CB2 antagonist delayed germ cell differentiation. Thus, both hyper‐ and hypostimulation of CB2 disrupted the temporal dynamics of the spermatogenic cycle. These findings highlight the importance of proper CB2 signaling for the maintenance of a correct temporal progression of spermatogenesis and suggest a possible adverse effect of cannabis in deregulating this process.—Di Giacomo, D., De Domenico, E., Sette, C., Geremia, R., Grimaldi, P. Type 2 cannabinoid receptor contributes to the physiological regulation of spermatogenesis. FASEB J. 30, 1453–1463 (2016). www.fasebj.org