The innervation and neuropeptide expression of fetal and infant human esophagus were studied. Esophageal samples (n = 30) from 8 weeks' gestation to 28 months of age were immunostained using antisera to general and specific neuronal antigens, and the results were quantified using computer-assisted image analysis. Nerve protein (protein gene peptide 9.5 and synaptophysin) and glial cell protein (S100) immunoreactivities were present by 8 weeks' gestation in primitive cell bodies and fibers in the outer layers of the esophagus. Immunoreactivity for peptides was first detected in fibers at 11 weeks' gestation in myenteric plexus and at 13 weeks' gestation in muscle. Peptide-immunoreactive cell bodies were not seen until 13-15 weeks. A pattern of immunoreactivity for neuropeptides comparable with that seen in mature neonates and infants was present by 22 weeks of gestational age. The percentage area of protein gene peptide 9.5-immunoreactive and vasoactive intestinal peptide-immunoreactive nerve fibers increased from low levels to 3.68% and 0.27%, respectively, at 13 weeks and peaked at 18 weeks (10.50% and 4.74%). These findings provide a foundation for future research into the contribution of neuropeptides to pediatric esophageal dysmotility.

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