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Updated: Dec 23, 2025
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
Prenatal low-dose endotoxin exposure prolongs intestinal epithelial activation after birth and contributes to
Hong-Yi Zhang1, Fang Wang2, Xinrao Meng1
1Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Purpose:
To investigate the effects of low dose endotoxin on transcriptional activity in intestinal epithelium, and its role in necrotizing enterocolitis (NEC).
Methods:
Lipopolysaccharides (LPS) were injected into the amniotic cavity of pregnant mice under ultrasound guidance. The effects of LPS on fetal and neonatal intestines were determined. Mouse pups were exposed to low dose LPS (0.01 μg per fetus) prenatally and subjected to experimental NEC after birth. The incidence and severity of NEC, as well as intestinal permeability, NF-κB activation, and IL-6 expression were studied. The signaling pathways in the intestinal epithelial cells (IECs) that were activated by LPS were also investigated.
Results:
Low dose LPS did not increase apoptosis, myeloperoxidase activity, histological injury or NF-κB activity in fetal intestines. However, prenatal low dose LPS exposure disturbed the transient and self-limited activation of NF-κB in neonatal intestines after birth. Importantly, it increased the incidence and severity of experimental NEC in neonatal mice. In primary IECs, low dose LPS induced IRAK-1 expression via activation of GSK3β. Elevated IRAK-1 levels prolonged the activation of IECs upon stimulation by high dose LPS.
Conclusion:
Prenatal low dose endotoxin exposure disturbs self-limited postnatal epithelial cell activation and predisposes the neonatal intestine to NEC.
Level Of Evidence:
Not applicable (experimental animal study).
