Protection of the Ovine Fetal Gut against <i>Ureaplasma</i>-Induced Chorioamnionitis: A Potential Role for Plant Sterols
Charlotte van Gorp,
Ilse H. de Lange,
Owen B. Spiller,
Frédéric Dewez,
Berta Cillero Pastor,
Ron M. A. Heeren,
Lilian Kessels,
Nico Kloosterboer,
Wim G. van Gemert,
Michael L. Beeton,
Sarah J. Stock,
Alan H. Jobe,
Matthew S. Payne,
Matthew W. Kemp,
Luc J. Zimmermann,
Boris W. Kramer,
Jogchum Plat,
Tim G. A. M. Wolfs
Affiliations
Charlotte van Gorp
Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands
Ilse H. de Lange
Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands
Owen B. Spiller
Cardiff University School of Medicine, Cardiff CF10 3AT, Wales, UK
Frédéric Dewez
Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, 6202 AZ Maastricht, The Netherlands
Berta Cillero Pastor
Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, 6202 AZ Maastricht, The Netherlands
Ron M. A. Heeren
Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, 6202 AZ Maastricht, The Netherlands
Lilian Kessels
Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands
Nico Kloosterboer
Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands
Wim G. van Gemert
Department of Surgery, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
Michael L. Beeton
Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff CF14 4XN, UK
Sarah J. Stock
MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK
Alan H. Jobe
Division of Neonatology/Pulmonary Biology, The Perinatal Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
Matthew S. Payne
Division of Obstetrics and Gynecology, School of Medicine, The University of Western Australia, Crawley WA 6009, Australia
Matthew W. Kemp
School of Women’s and Infant’s Health, The University of Western Australia, Crawley WA 6009, Australia
Luc J. Zimmermann
Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands
Boris W. Kramer
Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands
Jogchum Plat
Department of Nutrition and Movement Sciences, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6202 AZ Maastricht, The Netherlands
Tim G. A. M. Wolfs
Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands
Chorioamnionitis, clinically most frequently associated with Ureaplasma, is linked to intestinal inflammation and subsequent gut injury. No treatment is available to prevent chorioamnionitis-driven adverse intestinal outcomes. Evidence is increasing that plant sterols possess immune-modulatory properties. Therefore, we investigated the potential therapeutic effects of plant sterols in lambs intra-amniotically (IA) exposed to Ureaplasma. Fetal lambs were IA exposed to Ureaplasma parvum (U. parvum, UP) for six days from 127 d−133 d of gestational age (GA). The plant sterols β-sitosterol and campesterol, dissolved with β-cyclodextrin (carrier), were given IA every two days from 122 d−131 d GA. Fetal circulatory cytokine levels, gut inflammation, intestinal injury, enterocyte maturation, and mucosal phospholipid and bile acid profiles were measured at 133 d GA (term 150 d). IA plant sterol administration blocked a fetal inflammatory response syndrome. Plant sterols reduced intestinal accumulation of proinflammatory phospholipids and tended to prevent mucosal myeloperoxidase-positive (MPO) cell influx, indicating an inhibition of gut inflammation. IA administration of plant sterols and carrier diminished intestinal mucosal damage, stimulated maturation of the immature epithelium, and partially prevented U. parvum-driven reduction of mucosal bile acids. In conclusion, we show that β-sitosterol and campesterol administration protected the fetus against adverse gut outcomes following UP-driven chorioamnionitis by preventing intestinal and systemic inflammation.