Mouse model suggests proteins cause damage in fetal abdominal inflammation

Abdominal inflammation in human fetuses resulting from perforation of their intestines is likely caused by proteins in the fetus’ stool, according to a study from Kobe University that has established a new mouse model that will enable research and drug development for a condition that has been difficult to treat.

Fetal stools, called meconium, are sterile but still cause inflammation of the abdominal cavity when they leak from the intestine after perforation. Called meconium peritonitis, this is a potentially fatal condition for the baby, with a mortality rate of 10 to 15% in humans, and the cause and treatment have not been established.

Pediatrician Fujioka Kazumichi of Kobe University and his team therefore decided to reproduce the disease in mice.

Since the intestinal development of mice and humans is different, the intestine of a newborn mouse is equivalent to that of a human fetus after the 12th week of pregnancy, but even so, the mouse is too small and fragile to induce this condition through surgery.

So the research team created a slurry of meconium, which they collected from human newborns, and injected it into the pups’ abdominal cavity. They then characterized the resulting condition and compared the pups’ mortality rates in response to different treatments.

Their results, published in the journal Pediatric researchshow that mortality was not influenced by antibiotic treatment, ruling out a bacterial cause. However, when they heat-treated the meconium slurry before injection, which disrupts the natural shapes of the proteins, they found a significant reduction in mortality.

This indicates that proteins in meconium are responsible for the inflammation and, in particular, Archers speculate that the digestive enzymes abundant in meconium are the culprits.

The results of the Kobe University experiment also have broader implications. In another series of experiments, Fujioka and his team characterized the condition of the mouse pups after administration of meconium slurry by analyzing the mice’s biochemical and gene expression profiles.

By comparing these results to results from a previously established mouse model, in which puppies were injected with an extract of adult mouse intestinal contents, they were able to show that their model results in different symptoms.

Convinced that their model is likely to be specific to meconium-induced inflammation, the researchers argue that it is a suitable platform for conducting further research into this disease.

Fujioka and his team hope their work will lead to an effective treatment for the disease, which affects about one in 35,000 live births.

They conclude: “As our mouse model is simple and highly reproducible, it can be used in research to elucidate the pathophysiology of meconium peritonitis.”