• PMID: 26671998
• Gene Name: CNR2
• Condition: Regulation of spermatogenesis, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Regulation of spermatogenesis, Male infertility

Type 2 cannabinoid receptor contributes to the physiological regulation of spermatogenesis

Di Giacomo D, De Domenico E, Sette C, Geremia R, Grimaldi P.

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 CB2with the specific agonist JWH133 [3-(1',1'-dimethylbutyl)-1-deoxy-8-THC] (IC5010(-6)M) mimics epigenetic events induced by RA (IC5010(-7)M) in spermatogonia. Both JWH133 and RA treatments stimulate the expression of the meiotic genes c-KitandStra8, by up-regulating H3K4me3 and down-regulating H3K9me2 levels in genomic regions flanking the transcription start site. Moreover, both agents increase the expression ofPrdm9, the gene encoding a meiosis-specific histone, H3K4me3 methyltransferase, which marks hotspots 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 CB2antagonist delayed germ cell differentiation. Thus, both hyper- and hypostimulation of CB2disrupted the temporal dynamics of the spermatogenic cycle. These findings highlight the importance of proper CB2signaling 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. CI - © FASEB. FAU - Di Giacomo, Daniele AU - Di Giacomo D AD - *Department of Biomedicine and Prevention, Section of Anatomy, University of Rome "Tor Vergata," Rome, Italy; and Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy. FAU - De Domenico, Emanuela AU - De Domenico E AD - *Department of Biomedicine and Prevention, Section of Anatomy, University of Rome "Tor Vergata," Rome, Italy; and Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy. FAU - Sette, Claudio AU - Sette C AD - *Department of Biomedicine and Prevention, Section of Anatomy, University of Rome "Tor Vergata," Rome, Italy; and Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy. FAU - Geremia, Raffaele AU - Geremia R AD - *Department of Biomedicine and Prevention, Section of Anatomy, University of Rome "Tor Vergata," Rome, Italy; and Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy.