Phosphatidic acid phosphohydrolase and phospholipids in tracheal and amniotic fluids during normal ovine pregnancy

Samples of amniotic fluid and fetal tracheal fluid were obtained from 36 ovine pregnancies which were studied either acutely or chronically during the last two-thirds of gestation (65 to 149 days). The specific activity of phosphatidic acid phosphohydrolase (PAPase), disaturated lecithin (DS-L), total phospholipids (TLP) and the L/S ratio were assayed in the amniotic and tracheal fluids. There was a significant and progressive increase in the specific activity of PAPase in tracheal fluid beginning after 110 days, increasing from 66+/- 7 nmoles phosphate released X mg-1 protein x hour-1 (Mean +/- S.E.M.) less than or equal to 110 days, to 107 +/- 6 at 111 to 120 days, and to 277 +/- 70 at 131 to 144 days. The rise in PAPase specific activity was followed by a parallel rise in the DS-L fraction of the TPL (DS-L/TPL ratio), increasing from a DS-L/TPL ratio of 0.06 +/- 0.-1 in fetuses less than or equal to 120 days, to 0.29 +/- 0.06 at 121 to 130 days, and to 0.50 +/- 0.18 at 131 +/- 135 days. The PAPase specific activity and the L/S ratio in amniotic fluid did not change during pregnancy. Neonatal respiratory distress syndrome is the result of inadequate production of surface active material by the fetal and neonatal lung. The enzyme PAPase occupies a central role in the biosynthesis of the glycerophospholipids, and increases in the specific activity of PAPase in human amniotic fluid and in fetal rabbit lung tissue precede or are parallel with the increase in the L/S ratio and pulmonary surfactant synthesis, respectively. We have shown that this sequence is also demonstrable in ovine fetal tracheal fluid, thus providing an animal preparation in which the formation and regulation of surfactant biosynthesis during fetal lung maturation can be investigated in vivo.