Lung Growth Response after Tracheal Occlusion in Fetal Rabbits Is Gestational Age–Dependent

Paepe, Monique E. De; Johnson, Brian D.; Papadakis, Konstantinos A.; Luks, François I.

doi:10.1165/ajrcmb.21.1.3511

Cited by 79 publications

(67 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Possibilities include species differences, the method of inducing pulmonary hypoplasia (oligohydramnios vs. spinal cord section), the magnitude of change in distension, and the relative maturity of the lungs (10,36). Previous investigators have shown that pulmonary surfactant in fetal rats is increased by both endogenous (45) and exogenous glucocorticoids (38).…”

Section: Discussionmentioning

confidence: 99%

Effects of oligohydramnios on lung growth and maturation in the fetal rat

Kitterman

Chapin

Vanderbilt

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Oligohydramnios (OH) retards fetal lung growth by producing less lung distension than normal. To examine effects of decreased distension on fetal lung development, we produced OH in rats by puncture of uterus and fetal membranes at 16 days of gestation; fetuses were delivered at 21 or 22 days of gestation. Controls were position-matched littermates in the opposite uterine horn. OH lungs had lower weights and less DNA, protein, and water, but no differences in saturated phosphatidylcholine, surfactant proteins (SP)-A and -B, and mRNA for SP-A, -B, -C, and -D. To evaluate effects on epithelial differentiation, we used RTI 40 and RTII70, proteins specific in lung to luminal surfaces of alveolar type I and II cells, respectively. At 22 days of gestation, OH lungs had less RTI40 mRNA (P Ͻ 0.05) and protein (P Ͻ 0.001), but RTII70 did not differ from controls. With OH, type I cells (in proportion to type II cells) covered less distal air space perimeter (P Ͻ 0.01). We conclude that OH, which retards lung growth, has little effect on surfactant and impedes formation of type I cells relative to type II cells. fetal lung development; lung distension; pulmonary epithelial differentiation; pulmonary hypoplasia; pulmonary surfactant IN LATE GESTATION, the fetal lung undergoes marked changes in preparation for the transition to extrauterine life. These changes include growth, enlargement of distal potential air spaces, thinning of the septa, maturation of the surfactant system, and differentiation of distal pulmonary epithelium into mature alveolar type I and type II cells. Several studies have shown that fetal lung growth is controlled primarily by mechanical factors, especially distension of the lung (for reviews, see Refs. 26 and 29) and that maturation of the surfactant system is controlled primarily by endocrine factors (for reviews, see Refs. 3 and 48). In contrast, relatively little is known about factors that regulate differentiation of the alveolar epithelium.In 1977, Alcorn and associates (2) reported that tracheal ligation in fetal sheep, which increased lung distension, caused accelerated lung growth and a qualitative reduction in the number of alveolar type II cells; conversely, chronic drainage of tracheal fluid, which inhibited lung distension, retarded lung growth and increased the number of type II cells. However, they reported neither quantitative data for cell counts nor measurements of indicators of surfactant, which is produced by type II cells. Subsequently, other investigators have studied tracheal ligation in fetal sheep and have confirmed that an increase in lung distension results in a lower number of type II cells (6,11,37) and a higher percentage of type I cells (18). Tracheal ligation also results in lower concentrations in the lung of surfactant protein (SP)-A and saturated phosphatidylcholine (SatPC), the major surface-active lipid in pulmonary surfactant (28), as well as mRNA for SP-A, -B, and -C (32). Conversely, transection of the cervical spinal cord (which abolishes fetal breathing movemen...

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of oligohydramnios on lung growth and maturation in the fetal rat

Kitterman

Chapin

Vanderbilt

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Nuclei were stained with Hoechst. Results were expressed as the ratio of the pixel area of ␣-SMA staining (520 -530 nm) over the pixel area of the nuclei (15). Digital images were captured using the red channel to optimize contrast.…”

Section: Methodsmentioning

confidence: 99%

Identification of Cellular Processes That Are Rapidly Modulated in Response to Tracheal Occlusion Within Mice Lungs

et al. 2008

View full text Add to dashboard Cite

Lung development progresses through a process reliant on mechanical cell stretch. However, this process is not well defined at the molecular level. Our goal was to globally analyze the transcriptome of fetal mouse lungs following short periods of tracheal occlusion (TO) to identify cellular processes that are rapidly modulated in response to intraluminal stretch increase. Serial analysis of gene expression (SAGE) was used to examine the global transcriptomic response of mouse prealveolar stage lungs to in vivo TO at 1 and 3 h. SAGE results were extended by histo-and immunochemical examination. Based on the 97 TO-modulated transcripts identified, our results further point out that continuous stretch in developing lungs leads directly to rapid and highly specific phenotypic modifications in a significant proportion of pulmonary cells. We conclude that intraluminal stretch increase during prealveolar stage of lung development induces a critical transition of pulmonary cells phenotype in which there is an increase in ␣-smooth muscle actin A t the end of gestation, fetal lung volume is under the influence of an important and continuous distention that is secondary to the continuous intraluminal liquid secretion by the fetal lung epithelium (1). Within developing lungs, this liquid sequestration occurs by the active larynx closure during the apnea (1), which accounts for the major portion of late fetal life (2). Abnormal loss of lung liquid is detrimental to lung development (3). Indeed, fetal cervical cord transection, which results in a lack of coordination between larynx opening and diaphragmatic movements, thus allowing excessive loss of lung liquid during fetal breathing movements, leads to lung hypoplasia (4). Similarly, loss of larynx tonus (5) and bypass of the larynx by experimental tracheotomy (6) during fetal life are both associated with excessive lung liquid loss and severe lung hypoplasia. In contrast, stimulation of lung growth and development can be achieved by using tracheal obstruction techniques at an appropriate developmental stage (7). By sequestering intraluminal liquid, fetal tracheal occlusion (TO) amplifies continuous stretch. TO represents a unique in vivo methodology that facilitates examination of the natural three-dimensional mechanical forces effect on lung development.Although the relationship between the degree of fetal lung expansion and lung development is well established, the mechanisms involved are not well understood. We hypothesize that an increase in fetal lung stretch causes a stimulus that rapidly mediates gene expression before any change in fetal lung structure is observed. To investigate the mechanisms underlying stretch-induced lung maturation, we previously created an in vivo murine model of TO that demonstrated a significant structural acceleration of prealveolar stage lung growth and development in a 24-h period (8). With this model, we recently demonstrated that TO induces an immediate cellular response (9). Indeed, when compared with sham-TO and unoperated-o...

show abstract

“…However, using three well-established methods to detect apoptosis (light and electron microscopy, the nucleosomal ladder pattern of DNA digestion, and the detection of apoptotic cells in situ by the terminal deoxynucleotidyl transferase-mediated nick-end labeling method), a shift in apoptosis was observed from the mesenchymal tissue layer during the earlier stages of development (9) to both the epithelial and mesenchymal tissue layers during the canalicular stage of development and onward (10,11). Increasing AEC2 apoptosis coincided with a decrease in cell proliferation, implicating epithelial apoptosis as a significant contributor of lung remodeling during late gestational development (12,13). Throughout the embryonic stage of lung development, apoptosis was almost exclusively found in the peripheral mesenchyme in regions of new bud formation or in the mesenchyme underlying branch points that are the site of extensive epithelial branching morphogenesis and remodeling of interstitial tissue, allowing room for outgrowth of the lung bud (10,14).…”

Section: Apoptosis and Lung Developmentmentioning

confidence: 96%