1. Chorioamnionitis induces hepatic inflammation and time-dependent changes of the enterohepatic circulation in the ovine fetus.
- Author
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Heymans C, den Dulk M, Lenaerts K, Heij LR, de Lange IH, Hadfoune M, van Heugten C, Kramer BW, Jobe AH, Saito M, Kemp MW, Wolfs TGAM, and van Gemert WG
- Subjects
- Animals, Bile Acids and Salts blood, Bile Acids and Salts metabolism, Carrier Proteins genetics, Carrier Proteins metabolism, Chorioamnionitis blood, Chorioamnionitis pathology, Cytokines blood, Cytokines metabolism, Disease Models, Animal, Female, Fetus immunology, Gene Expression Regulation immunology, Hepatitis blood, Hepatitis pathology, Lipopolysaccharides administration & dosage, Lipopolysaccharides immunology, Liver immunology, Liver pathology, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Pregnancy, Premature Birth blood, Sheep, Domestic, Time Factors, Chorioamnionitis immunology, Enterohepatic Circulation immunology, Fetus blood supply, Hepatitis immunology, Premature Birth immunology
- Abstract
Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure. An ovine chorioamnionitis model was used in which circulatory cytokines and outcomes of the liver and EHC of preterm lambs were longitudinally assessed following IA administration of 10 mg LPS at 5, 12 or 24h or 2, 4, 8 or 15d before preterm birth. Hepatic inflammation was observed, characterized by increased hepatic cytokine mRNA levels (5h - 2d post IA LPS exposure) and increased erythropoietic clusters (at 8 and 15 days post IA LPS exposure). Besides, 12h after IA LPS exposure, plasma BA levels were increased, whereas gene expression levels of several hepatic BA transporters were decreased. Initial EHC alterations normalized over time. Concluding, IA LPS exposure induces significant time-dependent changes in the fetal liver and EHC. These chorioamnionitis induced changes have potential postnatal consequences and the duration of IA LPS exposure might be essential herein.
- Published
- 2021
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