Age-related changes in the neuromuscular development of the internal anal sphincter

Abstract

Purpose The internal anal sphincter (IAS) plays an important role in the pathophysiology of constipation and incontinence. We hypothesized that functional bowel obstruction in premature infants is because of a poorly developed IAS. We investigated the neuromuscular development of IAS in fetal, newborn, and adolescent pigs. Methods Paraffin sections of IAS from 5 different age groups, E60, E90, 1 day, 4, and 12 weeks old, were stained with protein gene product 9.5 (PGP9.5), α-smooth muscle actin ( α-SMA), caldesmon (CALD), calponin (CALP), and desmin (DES) antibodies. Quantification of results was performed by grading the density of immunostaining. Results The PGP9.5-positive ganglion cells were observed in the myenteric and submucosal region of the entire length of the IAS at E60. An increase in ganglion cell size and density was observed with increasing age. There were striking differences in the density of PGP9.5, α-SMA, DES, CALD, and CALP immunoreactive fibers between prenatal and postnatal period with gradient increase in the number of fibers from after birth to 12 weeks of age. Conclusion This study shows for the first time that there are age-related differences in the distribution of neurons and smooth muscle cell components in the IAS. The decreased expression of contractile and cytoskeleton proteins in smooth muscle cells together with decreased expression of neurons in the IAS in the perinatal period may lead to motility dysfunction causing functional intestinal obstruction seen in premature infants.