Gastroschisis is a congenital anomaly in which the intestines are expo
sed to amniotic fluid throughout fetal life. Previous studies in anima
l models have demonstrated smooth muscle thickening and decreased cont
ractility, epithelial dysfunction, and submucosal thickening. The pres
ent studies were done to further define the mechanism of submucosal ch
anges by investigating collagen deposition and gene expression in a ra
bbit model. Gastroschisis was surgically created in fetal rabbits at 2
4 days gestation (term is 31 days). Sham-operated and unoperated fetus
es served as controls. Fetuses were sacrificed and bowels were harvest
ed at 26, 28, and 31 days gestation, Animal weight and gross and histo
logic appearance were assessed, Submucosal collagen content was measur
ed using the van Geison stain. In situ hybridization of the expression
of alpha (1) procollagen RNA was done to determine the distribution a
nd source of submucosal collagen. At term, submucosal thickening was p
resent in animals with gastroschisis, associated with a significantly
increased collagen content. Collagen distribution was also more diffus
e in the gastroschisis animals than in controls. In situ hybridization
revealed procollagen expression in round cells located in the submuco
sa and not in smooth muscle. These cells did not resemble fibroblasts,
and their identity is uncertain, Experimental gastroschisis is charac
terized by submucosal thickening which is associated with changes in c
ollagen, including increased deposition and more diffuse distribution
in the submucosa. The cells responsible for production of procollagen
are round, nonfibroblast cells which are located in the submucosa and
not in the smooth muscle layer. These findings may have some importanc
e in understanding the mechanisms responsible for intestinal malfuncti
on in infants with gastroschisis. (C) 1996 Academic Press, Inc.