Cannabinoid receptor 1 (CB1) signaling participates in the triggering of preterm birth induced by LPS

CAROLINA MARVALDI; ANA M. FRANCHI; JULIETA A. SCHANDER; MANUEL L. WOLFSON; JULIETA AISEMBERG

Congreso; SSR Virtual 2020; 2020

Society for the Study of Reproduction

Endocannabinoid system (ECs) is one of several signaling pathways implicated in maternal-fetal interface, and endocannabinoids are involved in different aspects of physiopathology of reproduction. 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. In mice, it has been shown that one of the major causes of PTB is premature decidual senescence, which becomes more aggravated by an inflammatory stimulus. Our group developed a murine model of preterm labor, consisting of two injections of bacterial lipopolysaccharide (LPS), that produces an 85% of PTB in BALB/c mice. The aim of the present work was to evaluate if the ECs participates in LPS-induced preterm labor. For this purpose, we administrated two doses of bacterial lipopolysaccharide (LPS, 10ug/g of weight and 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 vs 81% CB1-WT).To dilucidated this protective effect of the absence of CB1 on the triggering of PTB, we first studied different inflammatory mediators in decidua 5h after the second dose of LPS. We observed that LPS receptor, TLR-4, protein levels were diminished in LPS treated mice (p