Abstract
Intestinal motility disorders are a major cause of morbidity after surgical repair of intestinal atresia of unknown mechanism. We hypothesized that interruption of antenatal peristalsis may disturb the normal development of the enteric nervous system. Using a series of neuronal (synaptophysin, neuronal nitric oxide synthase, neurofilaments) and nonneuronal markers (glial acidic fibrillary protein and c-Kit) and immunohistochemistry, we have defined developmental steps of the enteric nervous system in normal intestine (12 fetuses, 15 children, and 4 adults) and their alterations above and below the obstacle in 22 human intestinal atresia compared with age-matched controls. Antisynaptophysin antibody revealed the progressive conversion of the myenteric plexus from a continuous belt into regularly spaced ganglions during normal fetal gut development and, by contrast, the significantly delayed appearance of individual neuronal ganglions in the distal segments of atresia (p < 0.05). Staging using three other markers for neuronal (neurofilaments and neuronal nitric oxide synthase) and nonneuronal cells (glial acidic fibrillary protein) confirmed that maturation of the myenteric plexus was significantly delayed below atresia (p < 0.01). These results indicate that intestinal atresia impairs the development of the enteric nervous system and provide an anatomical substrate for the motility disorders observed after surgical repair. They point to the role of peristalsis in normal gut development and suggest that stimulation of peristalsis might be used to accelerate recovery.
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Abbreviations
- ENS:
-
enteric nervous system
- GFAP:
-
glial fibrillary acidic protein
- ICC:
-
interstitial cells of Cajal
- NF:
-
neurofilament
- nNOS:
-
neuronal nitric oxide synthase
- SIS:
-
staining index for synaptophysin
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Acknowledgements
The authors thank G. Pivert for technical assistance and T. Attié for helpful discussion.
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Supported by the Fondation de l'Avenir, the Association pour l'Etude de la Pathologie Pédiatrique, and the Fondation NRJ-Institut de France.
The Group for the Study of Intestinal Atresia from the Departments of Pediatric Surgery and Pathology of Hôpital Edouard Herriot, Lyon (J.P. Chappuis, R. Bouvier); Hôpital d'Enfants-La Timone, Marseille (J.M. Guys, J.F. Pellissier); Hôpital Gatien de Clocheville, Tours (H. Lardy, F. Fetissof); Hôpital Pontchaillou, Rennes (O. Azzis, M.P. Ramée); Hôpital Mère-Enfants, Nantes (G. Podevin, C. Laboisse); Hôpital Robert Debré, Paris (Y. Aigrain, M. Peuchmaur).
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Khen, N., Jaubert, F., Sauvat, F. et al. Fetal Intestinal Obstruction Induces Alteration of Enteric Nervous System Development in Human Intestinal Atresia. Pediatr Res 56, 975–980 (2004). https://doi.org/10.1203/01.PDR.0000145294.11800.71
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DOI: https://doi.org/10.1203/01.PDR.0000145294.11800.71
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