CONICET | Buscador de Institutos y Recursos Humanos

PROTECTIVE EFFECT OF PROGESTERONE (P) ON PREGNANCY LOSS DUE TO LPS J.Aisemberg, C. Vercelli, M Wolfson, S. Billi, M.L. Ribeiro, M Farina, A.M.Franchi CEFYBO (CONICET-UBA) Buenos Aires, Argentina. afranchi@mail.retina.ar In the early pregnancy, low doses of LPS (lipopolysaccharide) that reproduce most of the effects of sepsis without affecting maternal survival produce high percentage of embryonic resorption (ER). In a murine model of LPS-induced ER we have demonstrated that uterine and decidual nitric oxide (NO) and prostaglandins (PG) synthesis are augmented and that the serum levels of P are diminished. Also LPS was able to increase in vitro uterine and decidual synthesis of PGE, NO and TNFa and this effect was abrogated by P. The non-rejection of the fetus in normal pregnancies has been partially attributed to the presence of immunomodulatory molecules induced by P. We characterized the production of two of them: 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 blocked LIF increase stimulated by LPS. Anandamide (AEA), the major endocannabinoid studied so far, has a role in pregnancy but high levels correlate with abortion. 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 P abrogated this effect. Also P treatment blocked the increased synthesis of NO and iNOS expression due to LPS. These results suggest that several inflammatory molecules could participate in the mechanism of LPS-induced ER and that their modulation by P could be a useful tool to prevent early pregnancy loss.