Inflammation of the abdominal cavity in human fetuses resulting from intestinal perforation is likely caused by proteins contained in fetal feces, according to a study by Kobe University that establishes a new mouse model that allows research and drug development for a disease that would otherwise be difficult to address.
Fetal stool, called “meconium,” is sterile, but causes inflammation of the abdominal cavity when it leaks from the intestine after perforation. This is a condition called “meconium peritonitis,” which is life-threatening for the baby and has a mortality rate of 10% to 15% in humans, and neither the cause nor treatment has been established.
So Kobe University pediatrician FUJIOKA Kazumichi and his team decided to reproduce the disease in mice. Because the intestinal development of mice and humans is different, the intestine of a newborn mouse pup is equivalent to that of a human fetus after the 12th week of pregnancy, but even then, the mouse pup is too small and fragile to induce the disease by surgery. So the research team created a suspension of meconium, which they extracted from human newborns, and injected it into the pups’ abdominal cavity. They then characterized the resulting disease and compared the pups’ mortality rates in response to different treatments.
Their results, published in the journal Pediatric researchThey show that mortality was not affected by antibiotic treatment, ruling out a bacterial cause. However, when they heat-treated the meconium suspension before injection, which alters the natural shapes of the proteins, they found a significant reduction in mortality. This indicates that the proteins contained in meconium are responsible for the inflammation, and in particular, the researchers assume that the digestive enzymes that are abundant in meconium are to blame.
The Kobe University development also has more general implications. In a different set of experiments, Fujioka and his team characterized the condition of mouse pups after administration of meconium suspension by analyzing the mice’s biochemical and gene expression profiles. By comparing that to results from a previously established mouse model, in which pups were injected with an extract of intestinal contents from adult mice, they were able to show that their model produces different symptoms. The researchers, who believe their model is likely specific to the inflammation caused by meconium, argue that it is a suitable platform for further research into the disease.
Fujioka and his team hope that their work will lead to the search for an effective treatment for this disease, which occurs in approximately one in every 35,000 live births. They conclude their paper by saying: “As our mouse model is simple and highly reproducible, it can be used in research to elucidate the pathophysiology of meconium peritonitis.”
This research was supported by the Japan Society for the Promotion of Science (grants 18K15710 and 20K08229), the Morinaga Hoshi-kai Foundation, the Kawano Masanori Memorial Public Interest Incorporated Foundation for the Promotion of Pediatrics, and the Japan Foundation for Pediatric Research.