CHANGES IN LUNG EXPANSION ALTER PULMONARY DNA-SYNTHESIS AND IGF-II GENE-EXPRESSION IN FETAL SHEEP

Our aim was to determine the effect of short-term (7-days) alteration in fetal lung liquid volume on pulmonary DNA synthesis rates and insul in-like growth factor-II (IGF-II) mRNA levels. Fifteen chronically cat heterized fetal sheep were divided into three groups. In one, the trac hea was obstructed, in another lung liquid was drained by gravity, and the third group served as controls. After 7 days [H-3]thymidine was i njected into each fetus and 8 h later fetal tissues were collected. Fe tal lung-to-body weight rations and total lung DNA contents were great ly increased in fetuses with tracheal obstruction compared with contro l fetuses, whereas the drainage of lung liquid did not affect these me asurements. DNA synthesis rates in pulmonary tissue were significantly reduced from a mean control value of 153.3 +/- 25.1 disintegration pe r minute (dpm)/mug DNA to 57.2 +/- 8.6 dpm/mug DNA by lung liquid drai nage (P < 0.05) and were significantly increased to 236.0 +/- 24.0 dpm /mug DNA by tracheal obstruction (P < 0.05). Following tracheal obstru ction, lung IGF-II mRNA levels were increased to 177.0 +/- 18.2% (P < 0.05) of the mean value for control fetuses, whereas they were reduced to 56.1 +/- 71% of control in lung liquid-drained fetuses. We conclud e that altering fetal lung expansion has a potent and rapid effect on pulmonary DNA synthesis and that this effect may, in part, be mediated by an alteration in IGF-II gene expression.