D2 | Abstract 06
Annual NUTRIM Symposium 18 November 2020
FUNDAMENTAL SCIENCE
Intestinal goblet cell loss during chorioamnionitis in fetal lambs: mechanistic insights and postnatal implications
Charlotte van Gorp1, Ilse H de Lange1,2, Kimberly RI Massy1, Lilian Kessels1, Alan H Jobe3, Jack P M Cleutjens4, Matthew W Kemp5, Matthias Hütten1,6, Boris W Kramer1, Luc J Zimmermann1, Tim G A M Wolfs1,
1Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University;
2Department of Surgery, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University;
3Division of Neonatology/Pulmonary Biology, The Perinatal Institute, Cincinnati Children’s Hospital Medical Center;
4Department of Pathology, School for Cardiovascular Diseases (CARIM), Maastricht University;
5School of Women’s and Infant’s Health, The University of Western Australia; 6Neonatology, Department of Pediatrics, University Hospital Aachen
Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier and intestinal epithelial endoplasmatic reticulum (ER) stress. We investigated whether chorioamnionitis can already induce such alterations in utero.
Fetal lambs were intra-amniotically (IA) exposed to lipopolysaccharides (LPS) for 5h, 12h, 24h, 2d, 4d, 8d or 15d before premature delivery at 125d gestational age (GA). Gut inflammation, the number, distribution and differentiation of goblet cells, ER stress, and apoptosis were measured.
We found a biphasic reduction in goblet cell numbers at 24h-2d, and at 15d of IA LPS exposure. The second decrease in goblet cell numbers was preceded by intestinal inflammation, apoptosis and crypt intestinal epithelial ER stress and increased SPDEF-positive cell counts.
Our combined findings strongly suggest that reduced development of mature goblet cells due to ER stress driven apoptosis of maturating goblet cells is mechanistically involved in the reduction in goblet cell numbers in the course of chorioamnionitis. Since similar changes have been described in patients suffering from NEC, these findings are considered to be clinically important for understanding the predecessors of NEC.
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