Abnormalities of digestive tract innervation in rat fetus treated with ethylenethiourea

Sidney Pereira Pinto Lemos,Patrícia Veruska Ribeiro Barbosa Lemos,Silvio Romero Gonçalves E Silva,Fernando Leandro Dos Santos,José Luiz Martins,Valdemiro Amaro Da Silva Júnior

doi:10.1590/s0102-86502012000300007

Abstract

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. 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. 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. Severe nerve plexus abnormalities associated with muscle layer atrophy were observed throughout the gastrointestinal tract in newborn rats exposed to ethylenethiourea.

Highlights

With the need of better understanding about the changes of the myenteric plexus in the small intestine in fetuses with anorectal anomalies, this study evaluated changes in the myenteric plexus throughout the gastrointestinal tract induced by ingestion of ETU and the alteration that occurred concurrently in the muscle wall bowel
The 21 newborn rats in the experimental group presented a variety of abnormalities in the gastrointestinal tract, musculoskeletal system and spine
Musculoskeletal abnormalities were observed in 100% of the fetus rats in the experimental group

Summary

Introduction

Anomalies of intestinal nervous plexus, including Hirschsprung’s disease and dysganglionosis are related to defects associated with abnormal migration of the neuroblasts[1], but for such anomalies the explanation for the pathophysiology and embryological remains imperfectly understood[2] This diffuse reduction in the number of ganglion cells along the colon is often seen in chronic constipation, so this type of disease can be considered as a possible reason for chronic idiopathic constipation[3]. This group of diseases affects social and productive life by intervening in the planning and economy of the health system, as well as increased costs and productive force in the country[4] These abnormalities have been correlated with obstructive or subocclusive intestinal conditions that are unrelated to tumors, in cases of children with Hirschsprung’s disease, cases of idiopathic chronic constipation[5] and, postoperatively, cases of anorectal anomalies. In particular they have been correlated with cases of low anorectal anomalies that present a good prognosis regarding fecal incontinence but frequently evolve with constipation[6].

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Conclusion