Ontogeny of neuroendocrine cells in human fetal lung. I. An electron microscopic study

An electron microscopic study of human fetal lung was undertaken to describe the ontogeny of neuroendocrine (NE) cells and neuroepithelial bodies (NEBs) and to determine their relationships to the developing nervous system. Lungs of 34 fetuses and 22 newborns were examined. Putative NE cells appeared prior to 8 weeks of gestation but, by 10 weeks, differentiated into NE cells and NEBs. Between 13 and 24 weeks the number of NE cells and NEBs increased, and subpopulations of NE cells were identified: a small population of cells that reached from basement membrane to lumen and NE cells associated with an electron-dense epithelial cell. Material past 24 weeks of gestation was obtained from live-born infants who died at various postnatal ages. Much of this material represented acute pulmonary damage in which NE cells were difficult to identify. As chronic lung disease developed, NE cells, singly and in groups, were easily identified in regenerating conducting airways. Growing axons associated with both NE cells and NEBs appeared as early as 10 weeks of gestation. Rare cholinergic, adrenergic, and nonadrenergic-noncholinergic terminals were identified in contact with NE cells and deep within NEBs. Afferent axon terminals were not identified with certainty. The data presented demonstrate innervation to at least some NE cells and NEBs throughout fetal life. It has been proposed that NE cells and NEBs are intrapulmonary neuroreceptors with paracrine secretory function. The present study suggests more complicated mechanisms integrated with the autonomic nervous system, inducing reflex activity at the level of the central nervous system. A tropic role for NE cells in the developing and regenerating lung is proposed.