Dual effect of nitric oxide (NO) on Prostaglandins (PG) synthesis in lipopolysaccharide (LPS)-induced pregnancy loss.

FRANCHI AM; CERVINI M; BILLI S; AISEMBERG J

Madrid, España.

Congreso; 2nd Iberoamerican Congress on Neuroimmunomodulation.; 2007

International Society for Neuroimmunomodulation

NO at high concentrations, as those observed in sepsis, has toxic effects on embryos either itself as a free radical or producing potent oxidants. PG are abortive since they stimulate uterine contractility. In our murine early embryonic resorption model, LPS increased NO and PG synthesis at the implantation sites. LPS produced complete embryonic resorption (ER) (100%) at 24 h. The aim of this study was to determine the effect of NO on PGs production and ER. Thus, we analyzed the consequence of SNAP (NO donor) and COX inhibitors on ER. Balb/c females were injected with LPS 1mg/gr, SNAP 3 mg/Kg, Quercetin (peroxynitrite scavenger) 10 mg/Kg and Quercetin + LPS at day 7 of pregnancy. Uterine and decidual tissues were removed at different times to determine PG level by RIA, COX mRNA expression by RT-PCR and protein by western blot. On day 12 the percentage of ER was determined. We observed that PG augmented early post-treatment with SNAP and they decreased at 6 h. We found that uterine COX-2 mRNA augmented throughout the LPS treatment while protein levels decreased. SNAP and Quercetin + LPS as LPS alone produced 100% RE but COX inhibitors prevented it. These results suggest that 1) PGs might be playing a major role in our model of septic pregnancy loss and 2) a divergent effect of NO on their synthesis.