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Updated: Jun 9, 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
C-section and systemic inflammation synergize to disrupt the neonatal gut microbiota and brain development in a model
Cécile Morin1, Flora Faure2, Julie Mollet3
1Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France; Department of Obstetrics and Gynecology, AP-HP, Robert Debré Hospital, 75019 Paris, France.
Insights
Cesarean sections combined with perinatal inflammation worsen brain development in preterm infants. This synergy impacts gut microbes, brain connectivity, and neurodevelopmental outcomes, highlighting critical risks for very preterm neonates.
Area of Science:
- Neuroscience
- Developmental Biology
- Neonatology
Background:
- Infants born very preterm face high risks of neurodevelopmental disorders.
- Perinatal systemic inflammation and C-sections are common in very preterm births.
- Existing mouse models partially replicate preterm infant neurodevelopmental deficits.
Purpose of the Study:
- To investigate the synergistic effects of C-section and perinatal systemic inflammation on brain development.
- To characterize neuropathological, imaging, and behavioral outcomes in a novel mouse model.
Main Methods:
- Developed a mouse model using intraperitoneal IL-1β injections (postnatal days 1-5) to mimic perinatal inflammation.
- Compared outcomes between C-section and vaginal delivery groups, with and without IL-1β treatment.
- Assessed gut microbial diversity, circulating peptidoglycans, microglia/macrophage reactivity, myelination, and brain functional connectivity.
Main Results:
- C-sections exacerbated IL-1β-induced reductions in gut microbial diversity and increased circulating peptidoglycans.
- Synergistic effects led to abnormal microglia/macrophage reactivity and impaired myelination.
- Combined C-section and inflammation significantly reduced brain functional connectivity.
Conclusions:
- C-section delivery synergizes with neonatal systemic inflammation to cause severe brain maldevelopment and dysfunction.
- These findings are relevant to very preterm infants at high risk for neurodevelopmental disorders.
- The mouse model effectively replicates key deficits observed in preterm neonates.
Abstract:
Infants born very preterm (below 28 weeks of gestation) are at high risk of developing neurodevelopmental disorders, such as intellectual deficiency, autism spectrum disorders, and attention deficit. Preterm birth often occurs in the context of perinatal systemic inflammation due to chorioamnionitis and postnatal sepsis. In addition, C-section is often performed for very preterm neonates to avoid hypoxia during a vaginal delivery. We have developed and characterized a mouse model based on intraperitoneal injections of IL-1β between postnatal days one and five to reproduce perinatal systemic inflammation. This model replicates several neuropathological, brain imaging, and behavioral deficits observed in preterm infants. We hypothesized that C-sections could synergize with systemic inflammation to induce more severe brain abnormalities. We observed that C-sections significantly exacerbated the deleterious effects of IL-1β on reduced gut microbial diversity, increased levels of circulating peptidoglycans, abnormal microglia/macrophage reactivity, impaired myelination, and reduced functional connectivity in the brain relative to vaginal delivery plus intraperitoneal saline. These data demonstrate the deleterious synergistic effects of C-section and neonatal systemic inflammation on brain maldevelopment and malfunction, two conditions frequently observed in very preterm infants, who are at high risk of developing neurodevelopmental disorders.
