Inflammation in the abdominal cavity of human fetuses, often due to a perforated intestine, is likely triggered by proteins present in fetal stool. This conclusion comes from a new study conducted at Kobe University that has developed a mouse model to facilitate research and drug development for this challenging condition.
Inflammation in the abdominal cavity of human fetuses, often due to a perforated intestine, is likely triggered by proteins present in fetal stool. This conclusion comes from a Kobe University study that has created a new mouse model to facilitate research and drug development for this challenging condition.
The stool of a fetus, known as “meconium,” is normally sterile. However, when it leaks from the intestine due to a perforation, it can lead to inflammation in the abdominal cavity, a condition referred to as “meconium peritonitis.” This condition poses a serious risk to the baby, with a mortality rate of 10%-15% in humans, and there have been no established causes or treatments.
To explore this further, pediatrician FUJIOKA Kazumichi from Kobe University and his team decided to mimic this condition in mice. Given the differences in intestinal development between mice and humans—the intestines of newborn mice are comparable to those of human fetuses after 12 weeks of pregnancy—the team determined that the small size of the mouse pups made surgical induction of this condition impractical. Instead, they created a mixture of meconium sourced from human newborns and injected it into the abdominal cavities of the pups. They then assessed the condition that developed and monitored the mortality rates of the pups under various treatments.
As detailed in their publication in the journal Pediatric Research, the findings indicated that antibiotic treatment did not affect mortality rates, suggesting that bacteria are not the cause. However, when the meconium mixture was heat-treated prior to injection—thus changing the structures of its proteins—the mortality rate dropped significantly. This finding implies that the proteins in meconium, particularly digestive enzymes, are likely the reason behind the inflammation.
The implications of this research extend further. In additional experiments, Fujioka and his colleagues analyzed the biochemical and gene expression profiles of the mice pups after meconium administration. By comparing these results with those from a previously developed mouse model, where adult mice’s intestinal contents were injected, they identified differing symptoms. Their belief is that their model is specific to inflammation caused by meconium, making it a valuable tool for further research on this condition.
Fujioka and his team are optimistic that their findings will aid in the search for effective treatments for this condition, which occurs in roughly 1 in every 35,000 live births. They emphasize the potential of their simple and reproducible mouse model for advancing the understanding of meconium peritonitis in their concluding remarks.
This research received funding from 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.
