The endocannabinoid anandamide as a relevant participant contributing to the onset of labor

ACCIALINI PAULA; FARINA MARIANA

Congreso; IX Latin American Society of Placenta and Maternal-Fetal Interaction virtual meeting; 2022

The onset of human labour involves the action of a wide range of factors that enables the transition from uterine quiescence to contractility. In line with this, oxytocin (OT), prostaglandins and nitric oxide (NO) play a pivotal role in the functionality of the placenta as well as in the regulation of myometrial contractility. Among the different signals that contribute to labour, growing evidence indicates that Anandamide (AEA), one of the main endocannabinoids, is involved in regulating this process. Anandamide is produced in the placenta and a significant increase in plasma levels is observed in labouring women compared to patients undergoing cesarean section before the onset of labour.For the aforementioned, we aimed to elucidate the participation of endocannabinoids in the regulation of the most relevant molecules in the onset of labor.Placental samples were obtained from patients with labouring vaginal deliveries and from non-labouring elective cesarean sections. We showed the OTR is differentially expressed with the onset of labour and that vaginal delivery placentas produce higher levels of prostaglandins than cesarean section samples. Besides, no differences were observed in NOS activity between groups. Incubation of vaginal delivery placentas with anandamide increased prostaglandins concentration and decreased NOS activity. Antagonism of type-1cannabinoid receptor (CB1) did not alter the effect observed on NOS activity. Conversely, incubation of cesarean section placentas with anandamide reduced prostaglandins levels and enhanced OTR expression and NOS activity, the latter involving the participation of CB1. Furthermore, we observed a differential expression of the main components of the endocannabinoid system between placental samples, being the change in CB1 localization the most relevant finding. Our results suggest that prior to the onset of labour AEA is relevant for maintaining elevated placental NOS activity and low prostaglandins concentration, contributing to a quiescent state. On the other hand, changes in the expression of placental endocannabinoid system occur with labour. This could result in a decrease of nitric oxide production along with an increase in placental prostaglandins concentration, contributing to the contractile signals that stimulate labour. Anandamide´s dual action seems to depend on the molecular context of the placenta, in terms of the different scenario established by the molecules that regulate labour. We propose that AEA acts as a modulator in the placenta, contributing to the set of signals that participate in the onset of labour at term.