Related Experiment Video
Updated: May 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
Time-dependent effect of in utero inflammation: a longitudinal study in rats
Marie-Ève Roy-Lacroix1, Maxime Guérard, Maryse Berthiaume
1Department of Obstetrics and Gynecology, CRC E-Lebel - CHUS, Université de Sherbrooke, Sherbrooke, QC, Canada.
Insights
Fetal exposure to inflammation, like from lipopolysaccharides (LPS), for 12 hours or more significantly impairs pup neurological development and increases mortality. Timely delivery before this critical window is key to preventing brain damage.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Inflammation during pregnancy can negatively impact fetal development.
- Understanding the critical windows of vulnerability is crucial for neuroprotection.
Purpose of the Study:
- To investigate how the duration of fetal exposure to inflammation affects neurological outcomes in offspring.
- To identify a potential threshold for inflammatory exposure that leads to adverse neurological effects.
Main Methods:
- Pregnant rats were exposed to lipopolysaccharides (LPS) or vehicle at different time points (3, 6, 12, 24 hours) before cesarean section.
- Maternal serum and amniotic fluid were analyzed for cytokine levels.
- Pup motor activity was assessed using the open-field test, and brain histopathology was examined.
Main Results:
- Perinatal mortality increased with longer LPS exposure durations.
- Pups exposed to LPS for 12 hours showed significantly reduced motor activity compared to controls.
- Elevated levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) were observed in maternal blood after 3, 6, and 12 hours of LPS exposure.
Conclusions:
- A critical duration threshold for fetal exposure to inflammation exists, beyond which significant neurological damage can occur.
- These findings suggest that the timing of delivery relative to inflammatory exposure is critical for preventing adverse neurodevelopmental outcomes.
Objective:
To determine the impact of the duration of fetal exposure to inflammation on the neurological outcome of pups.
Method:
Time-pregnant Sprague-Dawley rats (n = 32) received intraperitoneal injection of lipopolysaccharides (LPS; 500 µg/kg), or an equivalent volume of vehicle 3, 6, 12 and 24 h before C-section. Maternal serum and amniotic fluid were tested for cytokines. Motor activity of resuscitated pups (n = 58) was analyzed using the open-field test (20 d). Brains were collected for histopathological examination.
Results:
Perinatal mortality increased with the duration of fetal exposure to LPS. All parameters tested with the open-field test were lower in the LPS 12 h exposure group compared to the control group (p < 0.05). Tissue inhibitor of metalloproteinase 1 (TIMP-1) was statistically increased in maternal blood after 3, 6 and 12 h of LPS injection (p < 0.05 versus control).
Conclusion:
A threshold of duration of exposure to inflammation is demonstrated, before which delivery should be performed in order to prevent brain damage.
