CONICET | Buscador de Institutos y Recursos Humanos

Inflammation is necessary both for normal pregnancy, but if it becomes too excessive it might cause pregnancy complications such as fetal resorption/miscarriage. In the early pregnancy, low doses of LPS that reproduce most of the systemic effects of sepsis produce high percentage of embryonic resorption. Progesterone (P) serum levels were diminished in the LPS treated animals and this hormone abrogated the augmentation uterine and decidual synthesis of PGE, NO and TNFa due to LPS. One of the mechanisms that participate in the non-rejection of the fetus is the presence of immunomodulatory molecules induced by P. So we characterized the uterine and decidual production of two of these molecules: PP14 (Progestagen-dependent endometrial protein) and LIF (Leukemia inhibitory factor). PP14 protein levels in LPS-treated animals were significantly lower than in control group while LIF mRNA expression was increased. P increased LIF mRNA expression in normal pregnant mice in vitro and it blocked LIF increase stimulated by LPS. We have evaluated if Anandamide (AEA), the major uterine endocannabinoid, participates in the mechanism of LPS-induced NO production. LPS treatment augmented AEA synthesis and decreased its degradation. Also antagonists of cannabinoid receptors blocked the augmentation of NO due to LPS suggesting that AEA could have an anti-inflammatory effect. Peripheral lymphocytes from pregnant mice had higher activity of FAAH (AEA metabolizing enzyme) than those from non pregnant animals. LPS inhibited FAAH activity and expression and the administration of P abrogated the effect of LPS.