Outside-in? XXXX in very preterm chronically catheterized @entity742 fetuses is not driven by cells in the fetal blood.

@entity825 @entity32 @entity742 @entity18733 @entity40675 @entity18730 @entity600 @entity281 @entity5845 @entity204 @entity526
BACKGROUND: The @entity600 (delivery before 37 weeks gestation) is a major contributor to the global burden of @entity5845 and @entity204 . The cause of @entity600 is complex, multifactorial, and likely dependent, at least in part, on the gestational age of the fetus. Intrauterine @entity281 is frequent in preterm deliveries that occur at <32 weeks gestation; understanding how the fetus responds to proinflammatory insult will be an important step towards early @entity600 prevention. However, animal studies of @entity281 and @entity32 in prematurity commonly use older fetuses that possess comparatively mature immune systems. OBJECTIVE: Aiming to characterize acute fetal responses to microbial agonist at a clinically relevant gestation, we used 92-day-old fetuses (62% of term) to develop a chronically catheterized @entity742 model of very preterm pregnancy. We hypothesized that any acute fetal systemic inflammatory responses would be driven by signaling from the tissues exposed to @entity526 lipopolysaccharide that is introduced into the amniotic fluid. STUDY DESIGN: Eighteen ewes that were carrying a single fetus at 92 days of gestation had recovery surgery to place fetal tracheal, jugular, and intraamniotic catheters. Animals were recovered for 24 hours before being administered either intraamniotic @entity526 lipopolysaccharide (n  = 9) or sterile saline solution (n  = 9). Samples were collected for 48 hours before euthanasia and necroscopy. Fetal inflammatory responses were characterized by microarray analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: Intraamniotic lipopolysaccharide reached the distal @entity825 within 2 hours. @entity40675 increased tracheal fluid @entity18733 within 2 hours and generated a robust inflammatory response that was characterized by @entity18730 signaling pathway activation and up-regulation of cell proliferation but no increases in inflammatory mediator expression in cord blood RNA. CONCLUSIONS: In very preterm @entity742 fetuses, lipopolysaccharide stimulates @entity32 in the fetal lung and fetal skin and stimulates a systemic inflammatory response that is not generated by fetal blood cells. These data argue for amniotic fluid-exposed tissues that play a key role in driving acute fetal and intrauterine inflammatory responses.
