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Updated: Jun 15, 2025
A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
A neonatal mouse model of meconium peritonitis generated using human meconium slurry
Mariko Ashina1, Takumi Kido1, Keisuke Shirai1
1Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Background:
Meconium peritonitis is a noninfectious chemical peritonitis that occurs following fetal intestinal perforation and leakage of meconium into the abdominal cavity. Because of the lack of appropriate animal models, its pathophysiology has not yet been elucidated. We aimed to create a neonatal mouse model of meconium peritonitis using human meconium slurry (MS).
Methods:
A stock MS solution prepared from fresh meconium obtained from healthy term infants was administered intraperitoneally to 4-d-old newborn mice. An MS LD40 was then administered, and changes in body weight, hematology, serum biochemistry, and immunomodulatory gene expression were determined. The MS was subjected to antibiotic treatment and heat inactivation to validate the content. Finally, comparisons with nonsurgical neonatal sepsis mouse models were performed.
Results:
Dose-dependent mortality rates were observed, with an LD40 of 200 µL/body weight established. Substantial hematological and hepatorenal abnormalities and increased inflammatory gene expression were observed. Although antibiotic treatment was ineffective, the survival rate was improved by enzymatic inactivation of MS. Importantly, the systemic responses to MS were distinct from those observed in neonatal sepsis model mice.
Conclusion:
The MS model closely reflects the pathology of human neonatal meconium peritonitis and maybe useful in research elucidating the pathophysiology of this condition.
Impact:
In this study, we generated a neonatal mouse model of meconium peritonitis through intraperitoneal administration of human meconium slurry. We clarified that the pathogenic agent in meconium slurry is mainly a digestive enzyme, and that the systemic responses elicited by meconium slurry were distinct from those in a neonatal sepsis mouse model. As our mouse model is simple and highly reproducible, it is useful for elucidating the pathophysiology of meconium peritonitis.
Insights
Researchers developed a neonatal mouse model for meconium peritonitis using human meconium slurry (MS). This model, distinct from sepsis, identified digestive enzymes as the primary pathogenic agent, aiding pathophysiology research.
Area of Science:
- Neonatology
- Peritonitis Research
- Animal Modeling
Background:
- Meconium peritonitis is a noninfectious chemical peritonitis resulting from fetal intestinal perforation.
- Pathophysiology remains unclear due to a lack of suitable animal models.
- This study aimed to establish a neonatal mouse model using human meconium slurry (MS).
Purpose of the Study:
- To create a reproducible neonatal mouse model of meconium peritonitis.
- To investigate the pathophysiology of meconium peritonitis.
- To differentiate the systemic response from neonatal sepsis.
Main Methods:
- Intraperitoneal administration of human meconium slurry (MS) to 4-day-old mice.
- Determination of LD40, hematological, biochemical, and gene expression changes.
- Validation of MS content via antibiotic and heat inactivation; comparison with sepsis models.
Main Results:
- A dose-dependent mortality was observed, with an LD40 of 200 µL/body weight.
- Significant hematological and hepatorenal abnormalities and increased inflammatory gene expression were noted.
- Enzymatic inactivation of MS improved survival, unlike antibiotic treatment, and responses differed from sepsis models.
Conclusions:
- The MS mouse model accurately reflects human neonatal meconium peritonitis pathology.
- Digestive enzymes in MS were identified as the primary pathogenic agents.
- This simple, reproducible model is valuable for elucidating meconium peritonitis pathophysiology.
