Prenatal Origins of Human Intrapulmonary Arteries

Abstract

Recent studies on the morphogenesis of the pulmonary arteries have focused on nonhuman species such as the chick and the mouse. Using immunohistochemical techniques, we have studied 16 lungs from human embryos and fetuses from 28 d of gestation to newborn, using serial sections stained with a panel of antibodies specific for endothelium, smooth muscle, and extracellular matrix proteins. Cell replication was also assessed. Serial reconstruction showed a continuity of circulation between the heart and the capillary plexus from at least 38 d of gestation. The intrapulmonary arteries appeared to be derived from a continuous expansion of the primary capillary plexus that is from within the mesenchyme, by vasculogenesis. The arteries formed by continuous coalescence of endothelial tubes alongside the newly formed airway. Findings were consistent with the pulmonary arterial smooth muscle cells being derived from three sites in a temporally distinct sequence: the earliest from the bronchial smooth muscle, later from the mesenchyme surrounding the arteries, and last from the endothelial cells. Despite their different origins, all smooth muscle cells followed the same sequence of expression of smooth muscle-specific cytoskeletal proteins with increasing age. The order of appearance of these maturing proteins was from the subendothelial cells outward across the vessel wall and from hilum to periphery. The airways would seem to act as a template for pulmonary artery development. This study provides a framework for studying the signaling mechanisms controlling the various aspects of lung development.

Human Embryonic Blood Vessels: What Do They Tell Us About Vasculogenesis and Angiogenesis?

“…The prevalence of vasculogenesis over angiogenesis in five to seven weeks embryos is also supported by our findings regarding the coexpression of CD34 and Ki67; our data showed that there were no proliferating endothelial cells in five weeks embryos, and in seven weeks embryos, proliferation of endothelial cells was inconstant. Our results support also the fact that lung arteries are formed by vasculogenesis while pulmonary capillaries are formed by angiogenesis (Hall et al, 2000).…”

Mesothelium contributes to vascular smooth muscle and mesenchyme during lung development

“…2 and 3). Another possibility is that there are two alternative sources of smooth muscle, the mesothelium and the splanchnic mesoderm-derived mesenchyme (3,(20)(21)(22). More detailed lineage tracing studies and analysis of the phenotypes of labeled and unlabeled cells in the walls of the blood vessels will be needed to distinguish between these possibilities.…”

Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins

“…During the embryonic and pseudoglandular phase of development (< 18 weeks' gestation), all airways to the level of the terminal bronchiole form by division. Around each terminal bud, capillaries develop and form the pulmonary circulation 14 . Thus the pattern of pulmonary arteries and veins depends on the airway branching.…”