RESUMO
Little is known about whether exposure of the fetus to alcohol alters pulmonary development or function. This study aimed to determine whether low-moderate ethanol (EtOH) exposure throughout gestation alters structural and non-respiratory functional aspects of the fetal and postnatal lung. Sprague-Dawley rats were fed an ad libitum liquid diet ±6% v/v EtOH daily throughout pregnancy, achieving a plasma ethanol (EtOH) concentration of 0.03%. Gene and protein expression was determined in pulmonary tissue collected from fetuses at embryonic day (E) 20 and adult offspring. The percentage of airspace and alveolar size was measured in pulmonary tissue collected at postnatal day (PN) 1. At E20, EtOH-exposed fetuses had decreased aquaporin 5 mRNA levels and a non-significant trend for decreased epithelial sodium channel type α; expression of other pulmonary fluid homeostatic and development genes and surfactant protein genes were not different between groups. At PN1, there was no difference between EtOH-exposed and control offspring in the distal airspace percentage or diameter. At 8 months, collagen type III α1 gene expression was upregulated in EtOH-exposed male offspring; this was associated with increased collagen deposition at 10 months. At 19 months, male EtOH-exposed offspring had a 25% reduction in the protein levels of surfactant protein B. The alterations observed in male EtOH-exposed offspring suggest chronic low-moderate prenatal EtOH-exposure during development may result in increased pulmonary fibrosis. Such an alteration would decrease the respiratory capacity of the lung.
RESUMO
Obstruction of the fetal trachea is a potent stimulus for fetal lung growth and may have therapeutic potential in human fetuses with lung hypoplasia. However, the effects of increased lung expansion on lung development near midgestation, which is the preferred timing for fetal intervention, have not been well studied. Our aim was to determine the effects of increased lung expansion on lung development at 75-90 d of gestation in fetal sheep. In three groups of fetuses (n = 4 for each), the trachea was occluded for either 10 [10-d tracheal occlusion (TO) group] or 15 d (15-d TO group) or left intact (control fetuses). TO for both 10 and 15 d caused fetal hydrops, resulting in significantly increased fetal body weights. Both periods of TO significantly increased total lung DNA contents from 99.8 +/- 10.1 to 246.0 +/- 5.3 and 246.9 +/- 48.7 mg in 10- and 15-d TO fetuses, respectively. TO for 10 and 15 d also increased airspace diameter, although the percentage of lung occupied by airspace was not increased in 10-d TO fetuses due to large increases in interairway distances; this resulted from a large increase in mesenchymal tissue. The interairway distances at 15 d of TO were reduced compared with the 10-d value but were still approximately 30% larger than control values. We conclude that TO at <90 d of gestation in fetal sheep induces a greater increase in lung tissue growth than later in gestation but also causes fetal hydrops and produces changes in lung structure that are not compatible with efficient gas exchange. Thus, increased lung expansion at a similar stage of development in human fetuses is unlikely to induce changes in lung development that would facilitate gas exchange after birth.