The prenatal porcine intestine has low transforming growth factor-beta ligand and receptor density and shows reduced trophic response to enteral diets

Sangild PT, Mei J, Fowden AL, Xu RJ. The prenatal porcine intestine has low transforming growth factor-beta ligand and receptor density and shows reduced trophic response to enteral diets. Am J Physiol Regul Integr Comp Physiol 296: R1053-R1062, 2009. First published January 21, 2009; doi:10.1152/ajpregu.90790.2008.-Transforming growth factor-beta (TGF-beta) plays a role in enterocyte proliferation control, cell differentiation, and immune regulation via binding to specific TGF-beta receptors (TGF-beta R) in the intestinal epithelium. Endogenous TGF-beta production is low in the intestine during the perinatal period, but some exogenous TGF-beta ligands are supplied by amniotic fluid intake in the fetus and by colostrum ingestion in the neonate. It is not clear, however, whether luminal TGF-beta receptors are present and functional at this critical time. We studied intestinal TGF-beta receptors by immunohistochemistry during the last 20% of gestation in pigs and in chronically catheterized fetuses following exposure to colostrum, milk, and amniotic fluid (control). In fetal pigs, the TGF-beta Rs were predominantly localized to the crypt epithelium, but staining intensity increased markedly just before term and shifted to the villous epithelium in newborn pigs, concurrently with marked increases in villous heights and crypt depths (+ 100-200%, P < 0.05). In contrast to previous observations in term newborn pigs, fetal pigs did not show any milk-induced change in TGF-beta receptor densities or localization, although a moderate increase in villous height was observed, relative to control (+25-50%, P < 0.05). We conclude that intestinal TGF-beta receptor density and localization are immature and unresponsive to TGF-beta containing milk diets in prenatal pigs. Immaturity of TGF-beta-mediated immune regulation may play a role in the increased sensitivity of preterm neonates to diet-induced intestinal inflammatory disorders.