The human lung during the embryonic period: vasculogenesis and primitive erythroblasts circulation

Abstract

Vascularization and blood cell circulation are crucial steps during lung development. However, how blood vessels are generated and when lung circulation is initiated is still a matter of debate. A morpho-functional analysis of pulmonary vasculature was done using human lung samples between 31 and 56 days postfertilization (pf). The immunolocalization and expression of CD31, CD34, FLT-1, KDR and the vascular growth factor (VEGF) were investigated. The results showed that at day 31 pf, a capillary plexus is already installed, and a few primitive erythroblasts were seen for the first time within the lumen of some blood vessels. Around day 45 pf, an increase in the amount of primitive erythroblasts was detected in the parenchyma surrounding the distal segment of the bronchial tree. The expression of FLT-1, KDR, CD31 and CD34 was observed in endothelial cells of the capillary plexus and the VEGF was detected in the endodermal epithelium. Our results support the hypothesis that the initial formation of the capillary plexus around the tip of the growing airway bud occurs by vasculogenesis, probably regulated by VEGF and KDR. We also showed a very early onset of blood circulation, starting from day 34 pf, concomitant with the generation of new lung buds. In addition, the increasing number of primitive erythroblasts from week 6 onward, associated with a change in the shape of the blood vessels, suggests a remodeling process and that the generation of new distal vessels at the tip of the lung bud occurs mainly by a process of angiogenesis.

Unique Aspects of the Developing Lung Circulation: Structural Development and Regulation of Vasomotor Tone

“…With the development of the circulation, a mesenchymal capillary plexus forms between the arteries and the veins. 5,6 A similar phenomenon has been found at day E10.5 in the mouse. 7 At the end of the pseudoglandular stage, all preacinar pulmonary and bronchial arteries are in place and correspond to the bronchial branching pattern in human lung.…”

“…Continuity between the heart and the capillary plexus of the lung occurs as early as day 34 of pregnancy in the human, with the artery extending from the outflow tract of the heart and the vein connecting to the prospective left atrium. With the development of the circulation, a mesenchymal capillary plexus forms between the arteries and the veins 5 , 6 . A similar phenomenon has been found at day E10.5 in the mouse 7 .…”

“…Angiogenesis is the formation of new blood vessels from preexisting ones 9 . There are currently three different postulations regarding pulmonary vascular development: one proposes that central angiogenesis occurs concurrently with peripheral vasculogenesis, 10 – 12 a second considers vasculogenesis as the primary process in the developing lung, 7 , 13 , 14 and the third suggests that distal angiogenesis may act as the mechanism for lung vascular morphogenesis 5 , 15 . These discrepant models may result, in part, from the lack of genetic tools for sophisticated cell lineage tracing as well as the lack of a time‐based simultaneous detection of related signaling profiles 9 …”

Analysis of bronchial and vascular patterns in left upper lobes to explore the genesis of mediastinal lingular artery and its influence on pulmonary anatomical variation

“…In previous studies on pulmonary morphology, the objects are mainly human embryo specimens [ 8 – 10 ], which brought direct evidence for the origins of some congenital anomalies and variations. Meanwhile, given the discrepancies of pulmonary morphology between embryo and adult, these researches still can't clarify the common variations that thoracic surgeons often meet during pulmonary surgery.…”

Shaping the brain vasculature in development and disease in the single-cell era

“…Subsequently, pial capillaries perforate the external glial limiting membrane and grow into the cerebral cortex (comparable to the formation of the INVP in mice) from the eighth week of gestation onwards 90 . Whereas the CNS is, after vasculogenic formation of the PNVP, predominantly vascularized by sprouting angiogenesis 27 , vascularization of non-CNS tissues mainly relies on vasculogenesis 91 , 92 , for reasons that remain elusive.…”