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Updated: Jan 1, 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
Characterization of an Adapted Murine Model of Intrauterine Inflammation-Induced Preterm Birth
Hannah C Zierden1, Jairo I Ortiz Ortiz2, Peter Dimitrion3
1The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland.
Insights
A new double distal injection (DDI) method using lipopolysaccharide (LPS) improves preterm birth (PTB) model reproducibility. This enhanced model provides more uniform uterine exposure, aiding research into inflammation-induced PTB causes and treatments.
Area of Science:
- Reproductive Biology
- Immunology
- Animal Models
Background:
- Preterm birth (PTB) affects millions of infants annually, with infection/inflammation causing over 25% of cases.
- Existing animal models using lipopolysaccharide (LPS) for intrauterine inflammation have limitations in reproducibility and potency.
- Understanding inflammation-induced PTB mechanisms is crucial for developing preventative therapies.
Purpose of the Study:
- To develop an improved mouse model for studying inflammation-induced preterm birth.
- To enhance the reproducibility and potency of LPS-induced intrauterine inflammation.
- To investigate the distribution and effects of LPS using different administration methods.
Main Methods:
- A novel double distal injection (DDI) technique was developed for LPS administration, contrasting with the traditional single proximal injection (SPI).
- In vivo imaging with Evans Blue Dye assessed the distribution uniformity of LPS.
- Endotoxin levels in vaginal lavage fluid and gene expression in myometrial tissue were analyzed.
Main Results:
- The DDI method demonstrated more uniform distribution of inflammatory stimulus compared to SPI.
- DDI resulted in a more consistent induction of PTB and a linear dose-response relationship.
- SPI led to higher endotoxin concentrations in vaginal lavage and significant overexpression of cervical remodeling genes, suggesting localized effects.
Conclusions:
- The DDI model offers improved reproducibility and uniform uterine exposure for studying inflammation-induced PTB.
- This enhanced model is valuable for investigating fetal outcomes and therapeutic interventions for PTB.
- The findings highlight the importance of administration technique in LPS-induced PTB models.
Abstract:
Preterm birth (PTB) affects nearly 15 million infants each year. Of these PTBs, >25% are a result of inflammation or infection. Animal models have improved our understanding of the mechanisms leading to PTB. Prior work has described induction of intrauterine inflammation in mice with a single injection of lipopolysaccharide (LPS). Herein, we have improved the reproducibility and potency of LPS in the model using two injections distal to the cervix. An in vivo imaging system revealed more uniform distribution of Evans Blue Dye using a double distal injection (DDI) approach compared with a single proximal injection (SPI). Endotoxin concentrations in vaginal lavage fluid from SPI dams were significantly higher than from DDI dams. At equivalent LPS doses, DDI consistently induced more PTB than SPI, and DDI showed a linear dose-response, whereas SPI did not. Gene expression in myometrial tissue revealed increased levels of inflammatory markers in dams that received LPS DDI compared with LPS SPI. The SPI group showed more significant overexpression in cervical remodeling genes, likely due to the leakage of LPS from the uterine horns through the cervix. The more reliable PTB induction and uniform uterine exposure provided by this new model will be useful for further studying fetal outcomes and potential therapeutics for the prevention of inflammation-induced PTB.
