The endocannabinoid system is involved in murine lipopolysaccharide (LPS)-induced embryonic resorption (ER).

VERCELLI C, AISEMBERG J, BILLI S, CERVINI M, RIBEIRO ML, FRANCHI AM.

Los Cocos, Córdoba, Argentina.

Simposio; III Simposio Latinoamericano de Interacción Materno Fetal y Placenta: de la Investigación a la Clínica (III SLIMP).; 2007

Nitric oxide (NO) fulfills important functions during pregnancy and has a role in implantation, decidualization, vasodilation and myometrial relaxation. However, at high concentrations, such as those that are produced in sepsis, NO has toxic effects as it is a free radical. Our previous results indicate that LPS is capable of producing embryonic resorption in mice due to NO increased production not only in uterus but also in decidua. Recent research has revealed that LPS induces AEA synthesis in murine macrophages and down-regulates fatty acid amide hydrolase (FAAH, AEA degrading enzyme). The aim of the present work was to determine the effect of LPS and AEA on early murine pregnancy. On day 7 of pregnancy female mice were sacrificed and uterus and decidua were separated in each implantation site. Tissues were incubated in the presence of a) LPS, b) AEA, c) LPS + AM251 (cannabinoid type 1 receptor antagonist) and d) LPS + SR144528 (cannabinoid type 2 receptor antagonist) and NO was measured in culture supernatants as NO3- plus NO2-. Both LPS and AEA were capable of increasing NO levels in both tissues and NO production induced by LPS was inhibited when decidua was incubated in the presence of AM251 as well as in the presence of SR144528. LPS-induced NO production in uterus was inhibited only in the presence of AM251. We also assessed AEA synthesis, the activity of FAAH and the protein expression of this enzyme by western blot in the presence/absence of LPS. Treatment with the endotoxin increased AEA synthesis and decreased FAAH activity and protein expression in uterus. On the other hand, LPS only increased FAAH activity in decidua.  The results presented here suggest that AEA could be an intermediate in LPS effect.