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Updated: Jun 15, 2026
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Fetal exposure to maternal inflammation interrupts murine intestinal development and increases susceptibility to
Timothy G Elgin1, Erin M Fricke2, Huiyu Gong1
1Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
Insights
Fetal exposure to inflammation impairs gut development and immunity in mice. This increases susceptibility to gastrointestinal injury later in life, potentially explaining necrotizing enterocolitis in preterm infants.
Area of Science:
- Perinatology
- Neonatology
- Gastroenterology
- Immunology
Background:
- Chorioamnionitis can negatively impact fetal development, leading to increased gastrointestinal (GI) pathology like necrotizing enterocolitis (NEC) in infants.
- The precise mechanisms linking fetal exposure to maternal inflammation (FEMI) and subsequent GI issues remain unclear.
Purpose of the Study:
- To investigate how FEMI affects the developing gut and its susceptibility to injury.
- To elucidate the immunological and cellular changes induced by FEMI.
Main Methods:
- Pregnant mice were exposed to lipopolysaccharide (LPS) to mimic FEMI.
- Offspring were assessed for growth, intestinal histology, immune cell populations (goblet and Paneth cells), and inflammatory markers at various postnatal ages.
- Susceptibility to secondary LPS-induced intestinal injury was evaluated.
Main Results:
- FEMI did not affect offspring growth but significantly reduced goblet and Paneth cell numbers.
- FEMI increased serum levels of inflammatory cytokines including IL-1β, IL-10, KC/GRO, TNF, and IL-6 in an IL-6 dependent manner.
- FEMI-exposed offspring showed increased susceptibility to LPS-induced intestinal injury.
Conclusions:
- FEMI impairs normal intestinal development by altering innate immunity components and increasing inflammation.
- These changes provide a potential mechanism for the higher incidence of NEC and other GI disorders observed in infants exposed to chorioamnionitis.
Abstract:
Fetal exposure to chorioamnionitis can impact the outcomes of the developing fetus both at the time of birth and in the subsequent neonatal period. Infants exposed to chorioamnionitis have a higher incidence of gastrointestinal (GI) pathology, including necrotizing enterocolitis (NEC); however, the mechanism remains undefined. To simulate the fetal exposure to maternal inflammation (FEMI) induced by chorioamnionitis, pregnant mice (C57BL/6J, IL-6-/-, RAG-/- or TNFR1-/-) were injected intraperitoneally on embryonic day (E)15.5 with lipopolysaccharide (LPS; 100 µg/kg body weight). Pups were delivered at term, and reared to postnatal day (P)0, P7, P14, P28 or P56. Serum and intestinal tissue samples were collected to quantify growth, inflammatory markers, histological intestinal injury, and goblet and Paneth cells. To determine whether FEMI increased subsequent susceptibility to intestinal injury, a secondary dose of LPS (100 µg/kg body weight) was given on P5, prior to tissue harvesting on P7. FEMI had no effect on growth of the offspring or their small intestine. FEMI significantly decreased both goblet and Paneth cell numbers while simultaneously increasing serum levels of IL-1β, IL-10, KC/GRO (CXCL1 and CXCL2), TNF and IL-6. These alterations were IL-6 dependent and, importantly, increased susceptibility to LPS-induced intestinal injury later in life. Our data show that FEMI impairs normal intestinal development by decreasing components of innate immunity and simultaneously increasing markers of inflammation. These changes increase susceptibility to intestinal injury later in life and provide novel mechanistic data to potentially explain why preterm infants exposed to chorioamnionitis prior to birth have a higher incidence of NEC and other GI disorders.
