Prophylactic Intra-Uterine β-Cyclodextrin Administration during Intra-Uterine Ureaplasma parvum Infection Partly Prevents Liver Inflammation without Interfering with the Enterohepatic Circulation of the Fetal Sheep

Cathelijne Heymans, Lara R. Heij, Kaatje Lenaerts, Marcel den Dulk, Mhamed Hadfoune, Chantal van Heugten, Owen B. Spiller, Michael L. Beeton, Sarah J. Stock, Alan H. Jobe, Matthew S. Payne, Matthew W. Kemp, Boris W. Kramer, Jogchum Plat, Wim G. van Gemert, Tim G. A. M. Wolfs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)


Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver. Therefore, we investigated whether an intra-amniotic (IA)Ureaplasma parvum(UP) infection affected the liver and enterohepatic circulation (EHC) and evaluated whether an IA administered plant sterol mixture dissolved in beta-cyclodextrin exerted prophylactic effects. An ovine chorioamnionitis model was used in which liver inflammation and the EHC were assessed following IA UP exposure in the presence or absence of IA prophylactic plant sterols (a mixture of beta-sitosterol and campesterol dissolved in beta-cyclodextrin (carrier)) or carrier alone. IA UP exposure caused an inflammatory reaction in the liver, histologically seen as clustered and conflated hepatic erythropoiesis in the parenchyma, which was partially prevented by IA administration of sterol + beta-cyclodextrin, or beta-cyclodextrin alone. In addition, IA administration of beta-cyclodextrin prior to UP caused changes in the expression of several hepatic BAs transporters, without causing alterations in other aspects of the EHC. Thereby, the addition of plant sterols to the carrier beta-cyclodextrin did not have additional effects.

Original languageEnglish
Article number1312
Number of pages11
Issue number5
Publication statusPublished - May 2020


  • Ureaplasma parvum
  • intra-uterine infection
  • chorioamnionitis
  • preterm birth
  • plant sterols
  • liver
  • enterohepatic circulation
  • sheep

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