THE CANNABINOID RECEPTOR CB1 IN NORMAL AND PATHOLOGICAL PLACENTA. IMPLICATIONS IN THE PATHOPHYSIOLOGY OF PREECLAMPSIA.

ETCHEVERRY TOMAS; SZPILBARG NATALIA; LEGUIZAMÓN, GUSTAVO; SARACO NORA; MARTÍNEZ NORA; FARINA MARIANA

Buenos Aires

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología; 2023

Introduction: The placenta serves essential roles during gestation, including endocrine functions, nutrient exchange, and immune modulation. In human gestation, maternal blood directly interacts with chorionic villi, primarily through the syncytiotrophoblast (STB). Proper syncytialization of the trophoblast is crucial for a successful pregnancy. However, pathological conditions like preeclampsia are associated with alterations in this process. Preeclampsia is a common pregnancy disorder characterized by hypertension and proteinuria. Its multifactorial origin is believed to be related to abnormal placentation, particularly inadequate remodeling of uterine spiral arteries by extravillous cytotrophoblasts, leading to irregular uteroplacental blood flow and intermittent hypoxia-reoxygenation (HR), causing oxidative stress. The endocannabinoid system (ECS), a cellular signaling network comprising endocannabinoids, cannabinoid receptors (CB1, CB2), and related enzymes, has been found to be altered in preeclamptic placentas. Objectives: Evaluate HR’s effect on CB1 receptor expression in normal human placentas.Investigate HR’s impact on CB1 expression and syncytialization in a villous cytotrophoblast model. Materials and Methods: Chorionic villi explants were obtained from normal and preeclamptic term placentas. The BeWo choriocarcinoma cell line was used to study villous cytotrophoblast and syncytialization. Villi explants from normal placentas and BeWo cells were subjected to HR. Results: Preeclamptic placentas exhibited significantly increased CB1 and CB2 expression compared to normal placentas. HR increased CB1 expression in chorionic villi explants. In BeWo cells, HR elevated CB1 and CB2 levels. HR and Met-AEA treatment reduced syncytialization markers in BeWo cells, which was prevented by CB1 blockade with SR141716 antagonist. Conclusions: HR mimics CB1 changes observed in preeclampsia, supporting its role in this disease. These changes are replicated in an isolated trophoblast model. Additionally, CB1 stimulation reduced syncytialization markers, suggesting increased CB1 may contribute to placental function alterations. TOPIC AREA: ENDOCRINOLOGY- METABOLISM - REPRODUCTION