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Expression of the endocannabinoid system and response to cannabinoid components by the human fetal testis

dc.rights.licenseopenen_US
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorDOCHEZ-ARNAULT, J
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorDESDOITS-LETHIMONIER, Christèle
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorMATIAS, Isabelle
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorEVRARD, B.
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorLAGARRIGUE, M
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorTOUPIN, M
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorLARDENOIS, A
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorCHALMEL, F
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorMAZAUD-GUITTOT, S
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorDEJUCQ-RAINSFORD, N
hal.structure.identifierInstitut de recherche en santé, environnement et travail [Irset]
hal.structure.identifierÉcole des Hautes Études en Santé Publique [EHESP] [EHESP]
dc.contributor.authorGELY-PERNOT, A
dc.date.accessioned2023-11-13T15:10:07Z
dc.date.available2023-11-13T15:10:07Z
dc.date.issued2023-07-11
dc.identifier.issn1741-7015en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/184744
dc.description.abstractEnBackground - Cannabis consumption by pregnant women continues to increase worldwide, raising concerns aboutadverse effects on fetal growth and deleterious impacts on the newborn, in connection with evidence of placentaltransfer of cannabis compound. Cannabis action is mediated by the endocannabinoid system (ECS), which expression is well established in the brain but unknown in the developing testis. The fetal testis, whose endocrine function orchestrates the masculinization of many distant organs, is particularly sensitive to disruption by xenobiotics. In this context, we aimed to determine whether cannabis exposure has the potential to directly impact the human fetal testis.Methods - We determined the expression of components of the ECS in the human fetal testis from 6 to 17 developmental weeks and assessed the direct effects of phytocannabinoids Δ9‑trans‑tetrahydrocannabinol (THC) and cannabidiol (CBD) on the testis morphology and cell functions ex vivo.Results - We demonstrate the presence in the human fetal testis of two key endocannabinoids, 2‑arachidonylglycerol (2‑AG) and to a lower level anandamide (AEA), as well as a range of enzymes and receptors for the ECS. Ex vivo exposure of first trimester testes to CBD, THC, or CBD/THC [ratio 1:1] at 10−7 to 10−5 M altered testosterone secretion by Leydig cells, AMH secretion by Sertoli cells, and impacted testicular cell proliferation and viability as early as 72 h post‑exposure. Transcriptomic analysis on 72 h‑exposed fetal testis explants revealed 187 differentially expressed genes (DEGs), including genes involved in steroid synthesis and toxic substance response. Depending on the molecules and testis age, highly deleterious effects of phytocannabinoid exposure were observed on testis tissue after 14 days, including Sertoli and germ cell death.Conclusions - Our study is the first to evidence the presence of the ECS in the human fetal testis and to highlight the potential adverse effect of cannabis consumption by pregnant women onto the development of the male gonad.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enCBD
dc.subject.enEndocannabinoids
dc.subject.enEndocrine disruptors
dc.subject.enEnvironmental factors
dc.subject.enGerm cell development and cancer
dc.subject.enHuman fetal exposure
dc.subject.enTHC
dc.subject.enTestis
dc.title.enExpression of the endocannabinoid system and response to cannabinoid components by the human fetal testis
dc.title.alternativeBMC Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1186/s12916-023-02916-5en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed37430350en_US
bordeaux.journalBMC Medicineen_US
bordeaux.page219en_US
bordeaux.volume21en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - U1215en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamChimie Analytiqueen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDLigue Contre le Canceren_US
bordeaux.import.sourcehal
hal.identifierhal-04165941
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccCC BYen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=BMC%20Medicine&rft.date=2023-07-11&rft.volume=21&rft.issue=1&rft.spage=219&rft.epage=219&rft.eissn=1741-7015&rft.issn=1741-7015&rft.au=DOCHEZ-ARNAULT,%20J&DESDOITS-LETHIMONIER,%20Christ%C3%A8le&MATIAS,%20Isabelle&EVRARD,%20B.&LAGARRIGUE,%20M&rft.genre=article


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