title: 2-Arachidonoylglycerol impairs human cytotrophoblast cells syncytialization: influence of endocannabinoid signalling in placental development.
abstract: A balanced cytotrophoblast cell turnover is crucial for placental development and anomalies in this process associated with gestational diseases. The endocannabinoid system (ECS) has emerged as a new player in several biological processes. However, its influence during placental development is still unknown. We report here the expression of the endocannabinoid 2-arachidonoylglycerol (2-AG) main metabolic enzymes in human cytotrophoblasts and syncytiotrophoblast. We also showed that 2-AG induced a decrease in placental alkaline phosphatase activity, human chorionic gonadotropin secretion and Leptin mRNA levels. Moreover, 2-AG reduced glial cell missing 1 and syncytin-2 transcription and the number of nuclei in syncytium. These effects were mediated by cannabinoid receptors and may result from 2-AG inhibition of the cAMP/PKA signalling pathway. Our data suggest that 2-AG may interfere with the biochemical and morphological differentiation of human cytotrophoblasts, through a CB receptor-dependent mechanism, shedding light on a role for the ECS in placental development.
authors.affiliation: Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Celular e Molecular da Universidade do Porto (IBMC), Porto, Portugal.
authors.forename: M A
authors.initials: MA
authors.lastname: Costa
authors.affiliation: Departmento de Bioquímica U38FCT, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; Center for Biotechnology and Fine Chemistry, School of Biotechnology, Portuguese Catholic University, Porto, Portugal.
authors.forename: E
authors.initials: E
authors.lastname: Keating
authors.affiliation: Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Celular e Molecular da Universidade do Porto (IBMC), Porto, Portugal.
authors.forename: B M
authors.initials: BM
authors.lastname: Fonseca
authors.affiliation: Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Celular e Molecular da Universidade do Porto (IBMC), Porto, Portugal.
authors.forename: N A
authors.initials: NA
authors.lastname: Teixeira
authors.affiliation: Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Celular e Molecular da Universidade do Porto (IBMC), Porto, Portugal. Electronic address: george@ff.up.pt.
authors.forename: G
authors.initials: G
authors.lastname: Correia-da-Silva
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D015726:Giant Cells / Q000166:cytology / Q000378:metabolism*; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D006063:Chorionic Gonadotropin; C518353:ERVFRD-1 protein, human; D063388:Endocannabinoids; D005989:Glycerides; D020738:Leptin; D011257:Pregnancy Proteins; C094503:glyceryl 2-arachidonate; D017868:Cyclic AMP-Dependent Protein Kinases; D000469:Alkaline Phosphatase
keywords: 2-arachinoylglycerol; Endocannabinoid signalling; Human cytotrophoblasts; Placenta; Syncytialization