Intestinal goblet cell loss during chorioamnionitis in fetal lambs: Mechanistic insights and postnatal implications

Charlotte van Gorp, Ilse H. de Lange, Kimberly R.I. Massy, Lilian Kessels, Alan H. Jobe, Jack P.M. Cleutjens, Matthew W. Kemp, Masatoshi Saito, Haruo Usada, John Newnham, Matthias Hütten, Boris W. Kramer, Luc J. Zimmermann, Tim G.A.M. Wolfs

Research output: Contribution to journalArticlepeer-review

Abstract

Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocol-itis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms underlying goblet cell alterations over time in an ovine chorioamnionitis model. Fetal lambs were intra-amniotically (IA) exposed to lipopolysaccharides (LPS) for 5, 12, or 24 h, or 2, 4, 8, or 15 d before premature delivery at 125 d 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 24 h–2 d after, and 15 d after IA LPS exposure. The second decrease of goblet cell numbers was preceded by intestinal inflammation, apoptosis, and crypt ER stress, and increased SAM-pointed domain-containing ETS transcription factor (SPDEF)-positive cell counts. Our combined findings indicated that ER stress drives apoptosis of maturating goblet cells during chorioamnionitis, ultimately reducing goblet cell numbers. As similar changes have been described in patients suffering from NEC, these findings are considered to be clinically important for understanding the predecessors of NEC, and targeting ER stress in this context is interesting for future therapeutics.

Original languageEnglish
Article number1946
Pages (from-to)1-17
Number of pages17
JournalInternational journal of molecular sciences
Volume22
Issue number4
DOIs
Publication statusPublished - 2021 Feb 2

Keywords

  • ER stress
  • Intestinal inflammation
  • Mucus barrier
  • Perinatal

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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