title: Chorioamnionitis induced hepatic inflammation and disturbed lipid metabolism in fetal sheep.
abstract: Chorioamnionitis frequently induces a fetal inflammatory response syndrome (FIRS), characterized by an elevation of proinflammatory 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) for 2 d or 2 wk 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 GA of 125 d (normal GA = 150 d). We found that 2 d after the endotoxin injections, inflammatory markers were significantly higher compared with controls. In addition, lipid and glucose metabolism were disturbed in response to endotoxin. Moreover, the antioxidant 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 (alanine aminotransferase and aspartate aminotransferase) were increased. In conclusion, chorioamnionitis induces liver inflammation leading to metabolic disturbances in the fetus.
authors: Department of Molecular Genetics and Pathology, Maastricht University, Maastricht 6200 MD, The Netherlands.
authors: Veerle
authors: V
authors: Bieghs
authors: Evi
authors: E
authors: Vlassaks
authors: Anne
authors: A
authors: Custers
authors: Patrick J
authors: PJ
authors: van Gorp
authors: Marion J
authors: MJ
authors: Gijbels
authors: Aalt
authors: A
authors: Bast
authors: Otto
authors: O
authors: Bekers
authors: Luc J I
authors: LJ
authors: Zimmermann
authors: Dieter
authors: D
authors: Lütjohann
authors: J-Willem
authors: JW
authors: Voncken
authors: A W Danilo
authors: AW
authors: Gavilanes
authors: Boris W
authors: BW
authors: Kramer
authors: Ronit
authors: R
authors: Shiri-Sverdlov
mesh_terms: D000818:Animals; D002821:Chorioamnionitis / Q000139:chemically induced / Q000503:physiopathology*; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000378:metabolism* / Q000473:pathology*; D006410:Hematopoiesis; D007249:Inflammation / Q000473:pathology* / Q000503:physiopathology*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy; D012756:Sheep
chemical_list: D004731:Endotoxins; D016209:Interleukin-8