title: The endocannabinoid anandamide impairs in vitro decidualization of human cells.
abstract: Endocannabinoids (eCBs) are endogenous mediators that along with the cannabinoid receptors (CB1 and CB2), a membrane transporter and metabolic enzymes form the endocannabinoid system (ECS). Several eCBs have been discovered with emphasis on anandamide (AEA). They are involved in several biological processes such as energy balance, immune response and reproduction. Decidualization occurs during the secretory phase of human menstrual cycle, which involves proliferation and differentiation of endometrial stromal cells into decidual cells and is crucial for the establishment and progression of pregnancy. In this study, a telomerase-immortalized human endometrial stromal cell line (St-T1b) and non-differentiated primary cultures of human decidual fibroblasts from term placenta were used to characterize the ECS using immunoblotting and qRT-PCR techniques. It was shown that St-T1b cells express CB1, but not CB2, and that both receptors are expressed in HdF cells. Furthermore, the expression of fatty acid amide hydrolase (FAAH), the main degrading enzyme of AEA, increased during stromal cell differentiation. AEA inhibited cell proliferation, through deregulation of cell cycle progression and induced polyploidy. Moreover, through CB1 binding receptor, AEA also impaired cell differentiation. Therefore, AEA is proposed as a modulator of human decidualization. Our findings may provide wider implications, as deregulated levels of AEA, due to Cannabis sativa consumption or altered expression of the metabolic enzymes, may negatively regulate human endometrial stromal cell decidualization with an impact on human (in)fertility.Free Portuguese abstract: A Portuguese translation of this abstract is freely available at http://www.reproduction-online.org/content/152/4/351/suppl/DC1.
authors: UCIBIO@REQUIMTELaboratório de Bioquímica, Departamento Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal.
authors: M
authors: M
authors: Almada
authors: UCIBIO@REQUIMTELaboratório de Bioquímica, Departamento Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal.
authors: C
authors: C
authors: Amaral
authors: UCIBIO@REQUIMTELaboratório de Bioquímica, Departamento Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal.
authors: M
authors: M
authors: Diniz-da-Costa
authors: UCIBIO@REQUIMTELaboratório de Bioquímica, Departamento Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal.
authors: G
authors: G
authors: Correia-da-Silva
authors: UCIBIO@REQUIMTELaboratório de Bioquímica, Departamento Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal.
authors: N A
authors: NA
authors: Teixeira
authors: UCIBIO@REQUIMTELaboratório de Bioquímica, Departamento Ciências Biológicas, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal brunofonseca@ff.up.pt.
authors: B M
authors: BM
authors: Fonseca
mesh_terms: D001095:Arachidonic Acids / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D010064:Embryo Implantation / Q000187:drug effects; D063388:Endocannabinoids / Q000494:pharmacology*; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D011247:Pregnancy; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C078814:anandamide