Gastroschisis in the rat model is associated with a delayed maturation of intestinal pacemaker cells and smooth muscle cells.
BACKGROUND
A pacemaker system is required for peristalsis generation. The interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and are identified by expression of the c-kit gene--encoded protein. Gastroschisis is characterized by a severe gastrointestinal dysmotility in newborns. In spite of this clinical picture, few studies have focused on smooth muscle cells (SMC) morphology and none on ICC. Therefore, their morphology has been studied in fetuses at term in the rat model of gastroschisis.


METHODS
At 18.5 day's gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of gastroschisis, and 10 underwent manipulation only. The small intestine of the latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit and actin (alpha smooth muscle antibody [alpha-SMA]) immunohistochemistry, and transmission electron microscopy (TEM).


RESULTS
In the controls, SMC were c-kit+ and alpha-SMA+, with labeling intensity increasing by age. At E21.5, some cells around the Auerbach's plexus were more intensely c-kit+, and differentiating ICC were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and alpha-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC. In the less-damaged loops, SMC were faintly c-kit+ and alpha-SMA+ and had ultrastructural features intermediate between those of E18.5 and E21.5 controls; ICC were very immature.


CONCLUSIONS
ICC and SMC differentiation is delayed in gastroschisis with the most damaged loops showing the most incomplete picture. These findings might help in understanding the delayed onset of peristalsis and the variable time-course of the recover seen in babies affected by gastroschisis.
Children's Institute for Surgical Science, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
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P
Midrio
M S
MS
Faussone-Pellegrini
M G
MG
Vannucchi
A W
AW
Flake
D000199:Actins / Q000032:analysis; D000818:Animals; D001683:Biological Clocks; D002454:Cell Differentiation; D003593:Cytoplasm / Q000648:ultrastructure; D005347:Fibroblasts / Q000473:pathology; D020139:Gastroschisis / Q000196:embryology* / Q000473:pathology*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000196:embryology / Q000473:pathology; D007421:Intestine, Small / Q000196:embryology* / Q000473:pathology*; D009130:Muscle, Smooth / Q000737:chemistry / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D000199:Actins; D019009:Proto-Oncogene Proteins c-kit