?Participation of nitric oxide, prostaglandins and endocannabinoids in a murine modelo of septic abortion?

ANA MARIA FRANCHI

dresden

Workshop; Internationale Vortragsreihe,; 2006

Universidad Carl Gustav Carus,

  Maternal infections are a cause of abort and preterm labor in humans but the mechanism of them are not clear. Spontaneous and cytokine-boosted abortion rates have been linked to exposure to LPS in the environment. In the early pregnancy, low doses of LPS that reproduce most of the systemic and cellular effects of sepsis, without affecting maternal survival, produce high percentage of embryonic resorption. We have observed that lipopolysaccharide (LPS) is capable of producing embryonic resorption in mice due to NO increased production. LPS also caused an increase in the oxidative damage, evidenced by nitration of tyrosine proteins, due to the peroxynitrite anion. Anandamide (AEA), the major endocannabinoid studied so far, has a role in implantation and embryo development. However, high levels of this molecule correlate with fetal weight loss and abortion. Recent research has revealed that LPS induces AEA synthesis in murine macrophages. So we evaluated if AEA participates in the mechanism of LPS-induced NO production on early murine pregnancy. On day 7 of pregnancy female mice were killed and uterus and decidua were separated in each implantation site. Uterus was then incubated for 24 h in the presence of a)LPS, b)AEA and c)LPS + AM251 or SR144528 (cannabinoid type 1 and 2 receptor antagonists, respectively) and NO was measured in culture supernatants. Both LPS and AEA were capable of increasing NO levels. The effect of LPS on NO production was dependent of co-incubation with AM251 but independent of co-incubation with SR144528. We also determined AEA synthesis, FAAH activity (AEA metabolizing enzyme) and the expression of this enzyme by PCR and western blot in the presence or absence of LPS. Treatment with the endotoxin increased AEA synthase activity and decreased FAAH activity and expression. These results suggest that AEA could participate in the mechanism of LPS-induced resorption.