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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.
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1 NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Department of Surgery, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
2 Maastricht University Medical Center+, Department of Surgery, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); University Hospital Aachen, Department of Surgery, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)
3 NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Department of Surgery, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); University Hospital Aachen, Department of Surgery, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507); University Hospital Aachen, Department of Pathology, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)
4 NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Department of Surgery, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Maastricht University, Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
5 Maastricht University, Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Maastricht University Medical Center +, Department of Pediatrics, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
6 The University of Western Australia, Division of Obstetrics and Gynecology, Crawley, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); The Perinatal Institute, University of Cincinnati, Division of Neonatology/Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA (GRID:grid.24827.3b) (ISNI:0000 0001 2179 9593)
7 The University of Western Australia, Division of Obstetrics and Gynecology, Crawley, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Tohoku University Hospital, Center for Perinatal and Neonatal Medicine, Sendai, Japan (GRID:grid.412757.2) (ISNI:0000 0004 0641 778X)
8 The University of Western Australia, Division of Obstetrics and Gynecology, Crawley, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Murdoch University, School of Veterinary and Life Sciences, Perth, Australia (GRID:grid.1025.6) (ISNI:0000 0004 0436 6763)
9 Maastricht University, Department of Pediatrics, School for Oncology and Developmental Biology (GROW), Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Maastricht University, Department of Biomedical Engineering (BMT), School for Cardiovascular Diseases (CARIM), Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099)
10 NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Department of Surgery, Maastricht, the Netherlands (GRID:grid.5012.6) (ISNI:0000 0001 0481 6099); Maastricht University Medical Center+, Department of Surgery, Maastricht, the Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382); University Hospital Aachen, Department of Surgery, Aachen, Germany (GRID:grid.412301.5) (ISNI:0000 0000 8653 1507)