Lack of cannabinoid receptor 1 decreases preterm birth rate: disbalance of decidual endocannabinoid system.

MARVALDI, CAROLINA; MIRÓN GRANESE, AYELEN AIXA; JOHNSON, CLARE ; SCHANDER, JULIETA AYLEN; AISEMBERG, JULIETA; CORREA, FERNANDO; BRADSHAW, HEATHER B; FRANCHI, ANA MARIA; WOLFSON, MANUEL LUIS

Santa Fe, New Mexico

Simposio; Keystone Symposia; 2023

Keystone symposia

Preterm birth (PTB) is the leading cause of morbimortality in neonates. The decidua is an essential tissue for preparing, establishing and maintaining pregnancy. A premature regression of the decidua is associated with preterm parturition. Endocannabinoid system (ECs) is one of several signaling pathways implicated in maternal- fetal interface, and endocannabinoids are implicated in different aspects of physiopathology of reproduction. We aimed to investigate decidual ECs in an inflammatory model of PTB and the effect of the lack of CB1 receptor.We developed a murine model of PTB induced by two ip. injections of LPS in CB1-KO mice. We observed that CB1-KO mice show lower PTB than WT mice (56% CB1-KO vs. 81,5% WT).We analyzed the histology of the maternal-fetal interface and observed that the decidua/placenta area was lower in LPS-treated mice in comparison with control, and the same pattern was observed both in WT and CB1-KO mice. Moreover, we observed that CB1-KO mice present higher junctional zone area in comparison with WT. We studied whether the ECs is modulated in CB1-KO mice deciduas after LPS treatment. We observed that LPS treatment diminishes CB2 receptor protein levels in CB1-KO mice. No differences were found on TRPV1 receptor protein levels. We observed no differences in protein levels on the enzyme that synthesizes AEA (NAPE-PLD) and the enzyme that degrades AEA (FAAH). However, we observed that CB1-KO deciduas present lower FAAH activity in comparison with WT deciduas. The same pattern response was found in control mice and LPS-treated mice. We also analyze levels of NAEs and 2-acyl-glycerols in decidual tissues. We found that NAEs (AEA, LEA and OEA) and 2-acyl-glycerols (2-OG, 2-LG and 2-AG) increase after LPS treatment in deciduas. Our results suggest that CB1 receptor is involved in the triggering of PTB and an LPS treatment results in a disruption of the ECs that impacts on the maternal-fetal interface physiopathology.