Effect of epidermal growth factor on lung growth in experimental fetal pulmonary hypoplasia

The purpose of this study was (1) to compare the expression of epithelial growth factor receptor (EGFR) in the lung tissues of human fetuses with or without pulmonary hypoplasia, and (2) to investigate the effects of EGF on lung growth in experimental pulmonary hypoplasia in rabbits. Firstly, we investigated the expression of EGFR in lung tissues of human fetuses with or without pulmonary hypoplasia by immunohistochemistry. Secondly, the amniotic fluid was shunted into the maternal abdominal cavity in a group of 12 fetal rabbits, another group (n = 12) received EGF injection (5 microg, i.p.) at day 25 of gestation. The third group (n = 12) was only treated with EGF while littermates not operated on served as the control group (n = 12). On day 29 of gestation, fetuses were delivered by Cesarean section and the lungs removed. The body weight and wet lung and liver weights were measured. As a measure of fetal lung growth, we determined the size of lung acini, the number of terminal airspaces, and diameter of alveoli (n = 6, each groups). We also measured the concentration of phosphatidylcholine (PC) and the lecithin/sphingomyelin (L/S) ratio in lung lavage fluid at birth in some fetuses (n = 6, each groups). In human fetuses with pulmonary hypoplasia, there was a significant decrease in radial alveolar count and expression of EGFR compared with fetuses without pulmonary hypoplasia. Amniotic shunt significantly decreased fetal lung/body weight ratio compared with control. Injection of EGF in the shunted group significantly increased lung/body weight ratio to the control level. The concentration of PC and L/S ratio in lung fluid lavage from rabbit fetuses with hypoplastic lungs was significantly higher than the other three groups. Histopathological examination of fetuses with hypoplastic lungs treated with EGF showed no significant change in the size of acini, number of terminal airspaces or the diameter of alveoli compared with the control group. Our results suggested that EGF was associated with lung growth and maturation of human lung and that treatment of rabbit fetuses with hypoplastic lungs with EGF facilitated lung growth and development.