Surfactant Protein A in Fetal Rats With Congenital Diaphragmatic Hernia

Abstract

Concentrations of disaturated phosphatidylcholine and surfactant protein A(SP-A) in amniotic fluid (AF) of pregnancies with fetuses that have congenital diaphragmatic hernia (CDH) are decreased (Am J OB Gyn 173, 1995). However, it is not well established if these abnormalities reflect alterations of fetal lung development or variations in the amount of AF. To distinguish between these possibilities we determined SP-A in fetal lungs from rats between 19-21 days of gestation (term=22 days), with or without CDH produced by maternal ingestion of the herbicide Nitrofen, and in the lungs of a control group of fetuses not exposed to Nitrofen. Using immunohistochemistry with an anti-human SP-A polyclonal antibody, SP-A was not detected in any fetal lung on day 19 of gestation. At 21 days of gestation there was abundant SP-A which appeared to be decreased in the air spaces of fetuses with CDH compared with fetuses without CDH or those not exposed to Nitrofen. To confirm these findings we used the same antibody for Western Blotting. A small amount of SP-A could be detected in the fetal lungs of the three groups without differences between them. At 21 days of gestation a marked decreased of SP-A was found in lungs from fetuses with CDH compared with the other groups (p<0.05 by ANOVA). Nonetheless, no differences were found between groups in the levels of mRNA for SP-A using a cDNA for human SP-A. These findings suggest that in rat fetuses with CDH there is decreased production of SP-A at post-translational levels. This abnormality probably explains the lower AF concentrations of SP-A found in human fetuses with CDH.