Chorioamnionitis induced hepatic inflammation and disturbed lipid metabolism in fetal sheep.

Chorioamnionitis frequently induces a fetal inflammatory response syndrome (FIRS), characterized by an elevation of pro-inflammatory mediators and systemic inflammation. Although there is increasing evidence that inflammation and lipid metabolism influence each other, the effects of chorioamnionitis-induced FIRS on fetal lipid homeostasis are currently not known. Accordingly, we hypothesize that chorioamnionitis induces an inflammatory response in the fetal liver, consequently leading to metabolic disturbances. Chorioamnionitis was induced by intra-amniotic injection of 10 mg endotoxin (control) two days or two weeks before delivery. Saline injections were given to controls. The effect of chorioamnionitis on hepatic inflammation and metabolic parameters was analyzed in ovine fetuses at the gestational age (GA) of 125 days (normal GA= 150 days). We found that two days after the endotoxin injections, inflammatory markers were significantly higher compared to controls. Additionally, lipid and glucose metabolism were disturbed in response to endotoxin. Moreover, the anti-oxidant state capacity was reduced and hepatic damage was apparent. Two weeks after the endotoxin injections the fetal livers were still inflamed and had higher glucose concentrations in the blood. In addition, the levels of markers for hepatic damage (ALT, AST) were elevated. In conclusion, chorioamnionitis induces liver inflammation, leading to metabolic disturbances in the fetus. ABBREVIATIONS: