Fetal intestinal obstruction induces alteration of enteric nervous system development in human intestinal atresia.
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.
Khen
Naziha
N
INSERM E-0212, Faculty Necker, 75743 Paris Cedex 15, France.
Jaubert
Francis
F
Sauvat
Frederique
F
Fourcade
Laurent
L
Jan
Dominique
D
Martinovic
Jelena
J
Vekemans
Michel
M
Landais
Paul
P
Brousse
Nicole
N
Leborgne
Michele
M
Nihoul-Fékété
Claire
C
Cerf-Bensussan
Nadine
N
Sarnacki
Sabine
S
D015415:Biomarkers; D017615:Enteric Nervous System / Q000002:abnormalities*; D005260:Female; D005315:Fetal Diseases / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007409:Intestinal Atresia / Q000209:etiology / Q000473:pathology*; D007415:Intestinal Obstruction / Q000150:complications / Q000473:pathology*; D007422:Intestines / Q000294:innervation / Q000473:pathology; D008297:Male; D009457:Neuroglia / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012189:Retrospective Studies
D015415:Biomarkers; D019009:Proto-Oncogene Proteins c-kit