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Published on: October 10, 2025
Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea
Sidney Pereira Pinto Lemos1, José Luiz Martins, Patrícia Veruska Ribeiro Barbosa Lemos
1Research and Surgery Program, Federal University of Sao Paulo, Brazil. sppls@hotmail.com
Insights
Exposure to ethylenethiourea in pregnant rats caused severe myenteric plexus abnormalities and muscle atrophy in offspring. These findings shed light on the pathophysiology of gastrointestinal conditions like Hirschsprung
Area of Science:
- Developmental biology
- Neuroscience
- Gastroenterology
Background:
- Myenteric plexus lesions are linked to intestinal conditions in children.
- Understanding the pathophysiology of these lesions is crucial for treating Hirschsprung's disease and related disorders.
Purpose of the Study:
- To investigate the effects of ethylenethiourea exposure on the fetal rat myenteric plexus.
- To evaluate myenteric plexus abnormalities in offspring of rats exposed to ethylenethiourea during pregnancy.
Main Methods:
- Female rats were exposed to ethylenethiourea or a control solution during pregnancy.
- Fetal digestive tracts were analyzed morphometrically and histopathologically.
- Frequencies of nerve plexus cells and interstitial cells of Cajal were assessed using specific markers.
Main Results:
- Offspring exposed to ethylenethiourea exhibited muscle and skeletal abnormalities, including anorectal anomalies and gastrointestinal atresias.
- Histopathological analysis revealed a thinner muscle layer with reduced frequencies of ganglion cells and interstitial cells of Cajal throughout the gastrointestinal tract.
Conclusions:
- Ethylenethiourea exposure during gestation leads to severe myenteric plexus abnormalities and muscle atrophy in developing rats.
- These findings provide insights into the developmental origins of certain congenital gastrointestinal disorders.
Purpose:
The pathophysiology of abnormalities associated with myenteric plexus lesions remains imperfectly understood. Such abnormalities have been correlated with subocclusive intestinal conditions in children with Hirschsprung's disease, cases of chronic constipation and, postoperatively, in cases of anorectal anomalies. This study evaluated abnormalities of the myenteric plexus in fetus from female rats that received ethylenethiourea.
Methods:
Female rats were exposed to ethylenethiourea on the 11(th) day of pregnancy (experimental group) or to 0.9% physiological solution (control group). Abnormalities were only found in the experimental group. The digestive tract muscle layer was analyzed morphometrically and changes to the frequencies of nerve plexus cells and interstitial cells of Cajal were evaluated, using hematoxylin-eosin, S-100 protein, neuron-specific enolase and C-Kit, respectively.
Results:
Muscle and skeletal abnormalities were observed in 100%, anorectal anomalies in 86%, absent tail in 71%, short tail in 29%, duodenal atresia in 5%, esophageal atresia in 5% and persistent omphalomesenteric duct in 5%. Histopathological analysis showed a thinner muscle layer associated with lower frequencies of ganglion cells and interstitial cells of Cajal, in all gastrointestinal tract.
Conclusion:
Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.

