ENDOCANNABINOID SYSTEM IS INVOLVED IN THE TRIGGERING OFPRETERM LABOR BY LPS

MARVALDI, CAROLINA; SCHANDER, JULIETA AYLEN; AISEMBERG, JULIETA; DE LA CRUZ, FERNANDA; FRANCHI, ANA MARIA; WOLFSON, MANUEL LUIS

CABA

Congreso; IFPA 2019- VIII SLIMP; 2019

Objectives:The aim of this study was to investigate the participation ofendocannabinoid system (ECs) in a lipopolysaccharide (LPS)-inducedpreterm labor model and design an ex-vivo approach to study the role ofECs in LPS-response.Methods:Prematurity is the leading cause of morbimortality in neo-nates and is well known that premature deliveries are associated withinfectious process. Our group developed an inflammatory murine modelinduced by administration of bacterial LPS that produces an 85% ofpreterm birth (PTB). Here, we evaluated cyclooxygenase 2 (COX-2)protein level and fatty acid amide hydrolase (FAAH, enzyme thatdegradates endocannabinoids) activity in deciduas and peripheral bloodmononuclear cells (PBMC). Also, we utilized an ex-vivo model, wheredeciduas from 15-day pregnant mice were obtained and cultured 6h or9h, in presence or absence of LPS or a cannabinoid receptors agonist(methanandamide, mAEA). COX-2 protein level and FAAH activity wereevaluated. Besides, we evaluated the PTB rate in cannabinoid receptor 1-KO mice (CB1-KO).Results:In deciduas from 15-day pregnant mice injected with LPS weobserved an increase in COX-2 protein levels vs deciduas from controlpregnant mice (p<0.05). FAAH activity was not modified by LPS treatmentin deciduas, however, it was diminished in PBMC (p<0.05).In cultured decidua explants from 15-day pregnant mice, we observed thatFAAH activity was increased after 9h of LPS treatment. Besides, weobserved that COX-2 protein expression increased when the explants wereincubated with LPS for 6h. Furthermore, in presence of mAEA, COX-2protein levels were increased vs. control (p<0.05).In this sense, we found that CB1-KO mice show lower PTB than WT CD1mice (53% CB1-KO vs 78% WT).Conclusion: In summary, these data suggest that endocannabinoid systemis involved in the pro-inflammatory response associated with LPS-inducedPTB and we designed an ex vivo model to further understand its partici-pation on decidual tissue.