CONICET | Buscador de Institutos y Recursos Humanos

Background and purpose: Maternal infections are one of the main causes of adverse developmental outcomes including embryonic resorption and preterm labor. The purpose was to develop a mouse model of inflammation-associated preterm delivery induced with bacterial lipopolysaccharides (LPS) and to study the relationship between nitric oxide (NO) and prostaglandins (PGs) in this model. Experimental approach: The murine model of preterm labor was set assaying different doses of LPS. Once established, it was used to analyze uterine prostaglandins E2 and F2á levels (radioimmunoassay), NO synthase (NOS) activity and ciclooxygenases (COX) and NOS proteins level (western blot). It was also studied if inhibitors of COX and NOS avoid LPS-induced preterm labor. In-vitro assays with a nitric oxide donor (SNAP) were performed to analyze the modulation of prostaglandins production by NO. Key results: LPS administration increased uterine NO and PGs synthesis and induced preterm delivery. The co-administration of meloxicam, a cyclooxygenase-2 inhibitor, or aminoguanidine, an inducible NOS inhibitor, prevented LPS-induced preterm delivery and blocked PGs and NO increase. Notably, it was found that the levels of NO determine its effect on PGs synthesis, since low concentrations of NO diminished PGs synthesis whereas high concentrations augmented them. Conclusions and implications: An infection-associated model of preterm labor showed that it can be prevented diminishing PGs or NO production. It was also determined that NO has a dual effect on PGs synthesis depending on its concentration. These contributions to the understanding of NO-PGs interactions in pregnancy and parturition could help to improve neonatal outcomes.