Journal article
Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development
PloS one, Vol.11(1), pp.e0146542-e0146542
2016
DOI: 10.1371/journal.pone.0146542
PMCID: PMC4706418
PMID: 26745886
Abstract
Infants with intrauterine growth restriction (IUGR) are at increased risk for neonatal and lifelong morbidities affecting multiple organ systems including the intestinal tract. The underlying mechanisms for the risk to the intestine remain poorly understood. In this study, we tested the hypothesis that IUGR affects the development of goblet and Paneth cell lineages, thus compromising the innate immunity and barrier functions of the epithelium. Using a mouse model of maternal thromboxane A2-analog infusion to elicit maternal hypertension and resultant IUGR, we tested whether IUGR alters ileal maturation and specifically disrupts mucus-producing goblet and antimicrobial-secreting Paneth cell development. We measured body weights, ileal weights and ileal lengths from birth to postnatal day (P) 56. We also determined the abundance of goblet and Paneth cells and their mRNA products, localization of cellular tight junctions, cell proliferation, and apoptosis to interrogate cellular homeostasis. Comparison of the murine findings with human IUGR ileum allowed us to verify observed changes in the mouse were relevant to clinical IUGR. At P14 IUGR mice had decreased ileal lengths, fewer goblet and Paneth cells, reductions in Paneth cell specific mRNAs, and decreased cell proliferation. These findings positively correlated with severity of IUGR. Furthermore, the decrease in murine Paneth cells was also seen in human IUGR ileum. IUGR disrupts the normal trajectory of ileal development, particularly affecting the composition and secretory products of the epithelial surface of the intestine. We speculate that this abnormal intestinal development may constitute an inherent "first hit", rendering IUGR intestine susceptible to further injury, infection, or inflammation.
Details
- Title: Subtitle
- Intrauterine Growth Restriction Alters Mouse Intestinal Architecture during Development
- Creators
- Camille M Fung - Division of Neonatology, Pediatrics, University of Utah, Salt Lake City, Utah, United States of AmericaJessica R White - Division of Neonatology, Pediatrics, University of Iowa, Iowa City, Iowa, United States of AmericaAshley S Brown - Division of Neonatology, Pediatrics, University of Utah, Salt Lake City, Utah, United States of AmericaHuiyu Gong - Division of Neonatology, Pediatrics, University of Iowa, Iowa City, Iowa, United States of AmericaJörn-Hendrik Weitkamp - Division of Neonatology, Pediatrics, Vanderbilt University, Nashville, Tennessee, United States of AmericaMark R Frey - Department of Pediatrics and Department of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine and The Saban Research Institute at Children's Hospital Los Angeles, Los Angeles, California, United States of AmericaSteven J McElroy - Division of Neonatology, Pediatrics, University of Iowa, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.11(1), pp.e0146542-e0146542
- DOI
- 10.1371/journal.pone.0146542
- PMID
- 26745886
- PMCID
- PMC4706418
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science
- Grant note
- R03 DK097335 / NIDDK NIH HHS DK095004 / NIDDK NIH HHS DK097335 / NIDDK NIH HHS T32 AI007343 / NIAID NIH HHS K08 HD061607 / NICHD NIH HHS AI007343 / NIAID NIH HHS DK083677 / NIDDK NIH HHS K08 DK083677 / NIDDK NIH HHS HD061607 / NICHD NIH HHS R01 DK095004 / NIDDK NIH HHS
- Language
- English
- Date published
- 2016
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093355502771
Metrics
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