Role of lung fluid volume in growth and maturation of the fetal sheep lung.

Moessinger, Adrien C.; Harding, Richard; Adamson, T. M.; Singh, Mongjam Meghachandra; Kiu, George

doi:10.1172/jci114834

Cited by 244 publications

(175 citation statements)

References 19 publications

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“…This has been demonstrated in both animal studies and in cases in which an infant suffered from congenital laryngeal atresia. [9][10][11] The respiratory cells responsible for fetal lung fluid secretion are believed to be alveolar cells, including type 1 and type 2, which constitute about 99% of the total lung epithelial surface area. Other airway cells, including Clara cells and ciliated surface epithelial cells, may have some role in fluid secretion as well.…”

Section: Fetal Lung Fluid Secretionmentioning

confidence: 99%

Clinical implication of lung fluid balance in the perinatal period

2011

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At birth, lung fluid produced during fetal life must be cleared immediately and efficiently before the first breath takes place, in order for infants to achieve a normal and successful transition from prenatal to postnatal life. Postnatal lung fluid resorption is mediated through activation of airway epithelial sodium channels (ENaC). The observation that ENaC expression is a gestational age-dependent process contributes to our understanding of the development of respiratory distress in both term and preterm infants due to impaired clearing of fluid from their lungs. As fluid absorption, mediated by ENaC activity, in postnatal life has a significant biological role in preventing respiratory distress, any strategy that enhances ENaC activity can potentially help to decrease its incidence and associated morbidity.

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Section: Fetal Lung Fluid Secretionmentioning

confidence: 99%

Clinical implication of lung fluid balance in the perinatal period

2011

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“…Prolonged obstruction of the fetal trachea, leading to the accumulation of pulmonary luminal liquid and overdistension of the lungs (13), results in pulmonary hyperplasia in rabbits (14) and sheep (15, 16); studies on the lungs of human infants with congenital laryngeal atresias have provided similar results (17, 18). In contrast, the prolonged removal of pulmonary liquid, preventing normal distension of the lungs, leads to pulmonary hypoplasia (15,16). In view of the sensitivity of the developing lung to its level of distension, we considered it possible that the reduced lung growth that follows the abolition of FBM could be caused by a prolonged change in thoracic, and therefore pulmonary, volume rather than by the absence of phasic thoracic and pulmonary movements.…”

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confidence: 99%

Abolition of Fetal Breathing Movements by Spinal Cord Transection Leads to Reductions in Fetal Lung Liquid Volume, Lung Growth, and IGF-II Gene Expression

1993

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ABSTRACT. Fetal breathing movements (FBM) are considered necessary for normal growth and structural maturation of the fetal lung, but the underlying mechanisms are unclear. The small fluctuations in lung dimensions caused by FBM have been proposed as a stimulus to lung growth, but it is equally possible that FBM act by maintaining the basal level of lung luminal volume, which is an established determinant of fetal lung growth. Our aim, therefore, was to determine the effects of abolishing FBM, while retaining the integrity of the diaphragm, on the volume and rate of production of fetal lung liquid, gene expression for IGF-11, and fetal lung growth. FBM were abolished in seven fetal sheep by high spinal cord transection at 114 f 1.2 d of gestation; seven intact fetuses served as controls. At 119 to 124, 125 to 130, and 131 to 136 d, we measured the volume and secretion rate of lung liquid by dye dilution. At these three age ranges, the lungs of cord-transected fetuses contained 27 to 53% less lung liquid than controls ( p = 0.004), and their rates of secretion were 65 to 138% greater (p = 0.001). At postmortem (135 f 0.1 d), the lungs of the cord transected fetuses contained less DNA per kg body weight and tended to be lighter and to contain less protein than controls. IGF-I1 gene expression in the lungs of cord-transected fetuses was significantly less than that in controls. We conclude that the abolition of FBM causes an initial reduction in the degree of lung expansion, which eventually leads to lung hypoplasia, possibly mediated by reduced IGF-I1 gene expression. FBM probably contribute to the maintenance of fetal lung liquid volume, and hence lung growth, by opposing the loss of lung liquid caused by the elastic properties of the lungs. hypoplasia. Experimental abolition of FBM by section of the phrenic nerves in fetal sheep (3-5) also results in hypoplasia and structural immaturity of the lungs. Because prolonged denervation of the diaphragm leads to atrophy of the diaphragm muscle, the associated lung hypoplasia could have resulted from upward displacement of the diaphragm and a reduction in thoracic volume. Thus. experiments were subsequently performed in fetal rabbits (6) and sheep (7) in which FBM were abolished, while the integrity of the phrenic nerves and diaphragm were retained. In these studies, the upper cervical spinal cord was transected, thereby avoiding diaphragmatic atrophy but preventing the rhythmic activation of phrenic motoneurons from brainstem respiratory neurons. These experiments (6, 7) resulted in pulmonary hypoplasia in the absence of diaphragmatic atrophy, leading to the suggestion (8-10) that the small fluctuations in thoracic and lung dimensions that are caused by FBM (1 1, 12) provide a necessary stimulus for normal lung growth and maturation. It has been known for many years that the degree of fetal lung distension by its luminal liquid is an important determinant of lung growth and structural maturation. Prolonged obstruction of the fetal trachea, leading to the accumulation o...

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“…It is well established that mechanical forces generated by constant distension pressure and fetal breathing movements are critical for normal fetal lung development (11). One of the potential mechanisms by which mechanical forces promote lung development is by the release of growth factors (50,51).…”

Section: Discussionmentioning

confidence: 99%

Strain-induced Differentiation of Fetal Type II Epithelial Cells Is Mediated via the Integrin α6β1-ADAM17/Tumor Necrosis Factor-α-converting Enzyme (TACE) Signaling Pathway

Wang

Huang

Nayak

et al. 2013

Journal of Biological Chemistry

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Background: Mechanical forces are critical for normal fetal lung development. Results: Force applied to ␣ 6 ␤ 1 integrin activates TACE and sheds HB-EGF and TGF-␣. Conclusion: Mechanical strain enhances binding of ␣6␤1 integrin to TACE to promote fetal type II cell differentiation. Significance: Learning how mechanical forces regulate fetal lung development is critical for the discovery of approaches to accelerate lung maturation.

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Role of lung fluid volume in growth and maturation of the fetal sheep lung.

Cited by 244 publications

References 19 publications

Clinical implication of lung fluid balance in the perinatal period

Clinical implication of lung fluid balance in the perinatal period

Abolition of Fetal Breathing Movements by Spinal Cord Transection Leads to Reductions in Fetal Lung Liquid Volume, Lung Growth, and IGF-II Gene Expression

Strain-induced Differentiation of Fetal Type II Epithelial Cells Is Mediated via the Integrin α6β1-ADAM17/Tumor Necrosis Factor-α-converting Enzyme (TACE) Signaling Pathway

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