{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:17:34Z","timestamp":1789827454967,"version":"4.0.1"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kinderonderzoeksfonds Limburg","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (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\u20132 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.<\/jats:p>","DOI":"10.3390\/ijms22041946","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T08:09:09Z","timestamp":1613462949000},"page":"1946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2920-9783","authenticated-orcid":false,"given":"Charlotte","family":"van Gorp","sequence":"first","affiliation":[{"name":"Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7780-9399","authenticated-orcid":false,"given":"Ilse H.","family":"de Lange","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands"},{"name":"Department of Surgery, School for Nutrition, Toxicology and Metabolism (NUTRIM), Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly R. I.","family":"Massy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Kessels","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan H.","family":"Jobe","sequence":"additional","affiliation":[{"name":"Division of Neonatology\/Pulmonary Biology, The Perinatal Institute, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 4522, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack P. M.","family":"Cleutjens","sequence":"additional","affiliation":[{"name":"Department of Pathology, School for Cardiovascular Diseases (CARIM), Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W.","family":"Kemp","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA 6009, Australia"},{"name":"Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai 980-8574, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruo","family":"Usada","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA 6009, Australia"},{"name":"Center for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai 980-8574, Miyagi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Newnham","sequence":"additional","affiliation":[{"name":"Division of Obstetrics and Gynecology, The University of Western Australia, Crawley, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"H\u00fctten","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris W.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc J.","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Oncology and Developmental Biology (GROW), Maastricht University, 6202 AZ Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4417-4144","authenticated-orcid":false,"given":"Tim G. 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