title: Transient receptor potential vanilloid 1 is expressed in human cytotrophoblasts: induction of cell apoptosis and impairment of syncytialization.
abstract: The normal development of placenta relies essentially on a balanced proliferation, differentiation and apoptosis of cytotrophoblasts. These processes are tightly regulated by several hormones, cytokines, lipids and other molecules and anomalies in these events are associated with gestational complications. The cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed in several organs and tissues and it participates in cellular events like nociception, inflammation and cell death. However, the expression and importance of this receptor in human placenta still remains unknown. In this work, we found that TRPV1 is expressed in human cytotrophoblasts and syncytiotrophoblasts. Furthermore, the TRPV1 agonists capsaicin and anandamide decreased cytotrophoblast viability and induced morphological alterations, such as chromatin condensation and fragmentation, which suggest the occurrence of apoptosis. Also, both TRPV1 agonists induced a loss of mitochondrial membrane potential and an increase of caspase 3/7 activity and production of reactive species of oxygen and nitrogen. Furthermore, capsaicin (10 μM) impaired the spontaneous in vitro differentiation of cytotrophoblasts into syncytiotrophoblasts by triggering TRPV1, as observed by the decrease in placental alkaline phosphatase activity and in human chorionic gonadotropin secretion. On the other hand, anandamide decreased placental alkaline phosphatase activity via a TRPV1-independent mechanism but did not influence the secretion of human chorionic gonadotropin. In conclusion, we showed that TRPV1 is expressed in human cytotrophoblasts and syncytiotrophoblasts and also reported the involvement of this receptor in cytotrophoblast apoptosis and differentiation.
authors.affiliation: Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular da Universidade do Porto (IBMC), Porto, Portugal.
authors.forename: M A
authors.initials: MA
authors.lastname: Costa
authors.affiliation: Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular da Universidade do Porto (IBMC), Porto, Portugal.
authors.forename: B M
authors.initials: BM
authors.lastname: Fonseca
authors.affiliation: Departamento de Bioquímica (U38-FCT), Faculdade de Medicina, Universidade do Porto, Porto, Portugal; Centro de Biotecnologia e Química Fina, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, 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 Molecular e Celular 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 Molecular e Celular 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: D017209:Apoptosis / Q000502:physiology; D001095:Arachidonic Acids / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D063388:Endocannabinoids / Q000494:pharmacology; D005260:Female; D006801:Humans; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011247:Pregnancy; D050916:TRPV Cation Channels / Q000819:agonists / Q000096:biosynthesis*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002211:Capsaicin; C078814:anandamide
keywords: Anandamide; Apoptosis; Capsaicin; Cytotrophoblasts; Syncytialization; TRPV1