Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200, MD, Maastricht, the Netherlands.
Department of Surgery, Maastricht University Medical Center+, 6202, AZ, Maastricht, the Netherlands.
Sci Rep. 2021 May 14;11(1):10331. doi: 10.1038/s41598-021-89542-4.
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.
绒毛膜羊膜炎，即胎儿膜的炎症，是早产的重要原因，也是导致包括败血症和肠道病变在内的不良新生儿结局的危险因素。肠道胆汁酸（BAs）积累和肝脏细胞因子产生与不良肠道结局有关。这些发现促使我们研究羊膜内（IA）脂多糖（LPS）暴露后肝脏和肠肝循环（EHC）的变化。本研究建立了羊的绒毛膜羊膜炎模型，在早产前 5、12 或 24 小时或 2、4、8 或 15 天 IA 给予 10mg LPS 后，纵向评估早产前胎羊循环细胞因子以及肝脏和 EHC 的结局。观察到肝脏炎症，表现为肝细胞因子 mRNA 水平升高（IA LPS 暴露后 5 小时至 2 天）和红细胞生成簇增加（IA LPS 暴露后 8 天和 15 天）。此外，IA LPS 暴露后 12 小时，血浆 BA 水平升高，而几个肝脏 BA 转运体的基因表达水平降低。最初的 EHC 改变随着时间的推移而趋于正常。总之，IA LPS 暴露会导致胎儿肝脏和 EHC 发生显著的时间依赖性变化。这些绒毛膜羊膜炎引起的变化可能具有产后的影响，IA LPS 暴露的持续时间在此过程中可能至关重要。
