INVESTIGADORES
FARINA Mariana
congresos y reuniones científicas
Título:
INVOLVEMENT OF THE ENDOCANNABINOID SYSTEM IN THE REGULATION OF OXYTOCIN RECEPTOR IN HUMAN PLACENTA
Autor/es:
ACCIALINI, P; ETCHEVERRY, T; ABAN, C; NEGRI MALBRÁN, M.; LEGUIZAMÓN, G.; MATE, S; FARINA, M
Reunión:
Congreso; XX Jornadas Anuales de la Sociedad Argentina de Biología (SAB). Segundas Jornadas Rioplatenses de Biología; 2018
Resumen:
The onset of labour is a process controlled by fetal, maternal and placental factors. Among the different signals that contribute to labour, oxytocin (OT) is produced not only by the hypothalamus but also by uterus, amnion and placenta. The synthesis of OT and the expression of its receptor (OTR) are increased in placenta at term. Interestingly, changes in OTR expression, rather than the concentration of OT, are considered important for labour onset and progression. Growing evidence indicates that the endocannabinoid system (ECS) is involved in regulating the initiation of labour. Endocannabinoids are a family of lipid-signaling molecules that regulate different physiological processes in the placenta, being Anandamide (AEA) the most relevant one. It exerts its main effects through two cannabinoid receptors: type 1 (CB1) and type 2 (CB2). Besides, some of its effects are achieved through a transient receptor potential vanilloid type 1 (TRPV-1). Anandamide is produced in the placenta and a significant increase in plasma levels are observed in labouring women with respect to patients undergoing cesarean section. Notably, AEA can trigger the release of OT in the rat hypothalamus, suggesting a possible relation between the ECS and OT/OTR signaling. Based on the aforementioned, we hypothesize that the ECS modulates the OT/OTR signaling in human placenta at term. The objectives were: 1) to study the expression of the ECS in human placenta from vaginal delivery (VD) or cesarean section (CS) at term, and 2) to analyze the effect of AEA on OTR expression in placenta at term. To this purpose, placentas from VD or CS were used for RT-qPCR, Western Blot and enzymatic activity. We found a significant decrease (p<0.05) in the mRNA and protein levels of FAAH, the enzyme that degrades AEA, in VD placentas. Moreover, we found a significant decrease (p<0.05) in its enzymatic activity, in agreement with the increase in AEA levels observed in labouring women. With respect to the endocannabinoids receptors, we found no differences in CB1 protein content between VD and CS placentas, while TRPV-1 protein levels were significantly lower (p<0.05) in VD placentas. Besides, explants from CS placentas were cultured in the presence of different concentrations of R-(+)-Methanandamide (Met-AEA), a stable AEA analogous, for 3 or 20 hours. Our preliminary results suggest that CS placentas present a basal lower OTR expression compared to VD placentas. Besides, the culture of CS placentas with Met-AEA for 20 hours produced a significant increase in OTR expression (p<0.05). Our findings indicate a differential expression of the ECS between VD and CS placentas, and suggest that EAE may modulate OTR expression in the placenta at term.