Cannabinoid receptor 1 (CB1) is involved in preterm birth induced by LPS

CAROLINA MARVALDI; JULIETA A. SCHANDER; JULIETA AISEMBERG; FERNANDA DE LA CRUZ; ANA M. FRANCHI; MANUEL L. WOLFSON

Mar del Plata

Congreso; Reunión conjunta S A I C . S A F E . S A B . SAP 2 0 1 9; 2019

S A I C . S A F E . S A B . SAP

Endocannabinoid system (ECs) is one of several signaling pathways implicated in maternal-fetal interface, and endocannabinoids are implicated in different aspects of physiopathology ofreproduction. Preterm birth (PTB) is the leading cause of mortality and morbidity in neonates.It is well known that premature deliveries are mainly associated with infectious process. Inmice, it has been shown that one of the major causes of PTB is premature decidualsenescence, which becomes more aggravated by an inflammatory stimulus.Our group developed a murine model of preterm labor, consisting of two injections ofbacterial lipopolysaccharide (LPS), that produces an 85% of PTB in BALB/c mice. The aim of thepresent work was to evaluate if the ECs participates in LPS-induced preterm labor. For thispurpose, we administrated two doses of bacterial lipopolysaccharide (LPS, 10ug/g of weightand 3h later 20ug/g of weigh respectively) on day 15 of pregnancy to CD1-wild type mice (CB1-WT) and CD1-knock out mice for the cannabinoid receptor 1 (CB1-KO).We found that CB1-KO mice show lower PTB percentage than CB1-WT mice (60% CB1-KO vs81% CB1-WT).We studied different inflammatory mediators in decidua 5h after the second dose of LPS andobserved that protein levels of TLR-4 were decreased in LPS treated mice (p<0.05) while CD14and COX-2 protein levels were augmented (p<0.05). The same response pattern was observedboth in CB1-WT and CB1-KO mice.It has been reported that disruption of autophagy balance (either increase or decrease) canlead to PTB. We evaluated decidual protein expression of LC3b II, a marker of autophagy, andobserved that CB1-KO mice presented lower decidual protein levels of LC3b II when comparedto CB1-WT (p