DELAYED HYDROPHOBIC SURFACTANT PROTEIN (SP-B, SP-C) EXPRESSION IN FETUSES OF STREPTOZOTOCIN-TREATED RATS

Tissues from fetuses and neonates of control and streptozotocin (STZ)-treated Sprague-Dawley rats were used to study the content and distribution of the hydrophobic surfactant protein B (SP-B) and the mRNAs for SP-B and SP-C using immunohistochemistry, RNA blotting, and tissue in situ hybridization. A dose of 50 mg/kg STZ was used to treat female rats before mating. The fetuses were sacrificed at fetal days 18 through 21 and neonates were obtained on neonatal days 1 and 2 (day of birth = end of day 22). At fetal day 18, SP-B was barely detectable by immunohistochemistry in control animals but die levels were progressively increased through gestation and easily detected by fetal day 21. At all fetal ages, SP-B was decreased in the STZ group compared with control animals. Both SP-B and SP-C mRNA were detectable at fetal day 18 in the control group and increased with advancing gestational age. In fetal lungs from the STZ group, SP-B and SP-C mRNA also showed an increase with advancing gestational age, but the levels were decreased compared with controls at fetal days 18, 20, and 21 (P < 0.05). At fetal day 19, this difference did not achieve statistical significance. Differences between the two groups were no longer detected by neonatal days 1 and 2. The difference between the STZ and control groups, in both protein (SP-B) and mRNA (SP-B and SP-C), diminished with advancing fetal age but remained significant up to fetal day 21. These data suggest that diabetes induced by STZ treatment interferes with normal expression of the hydrophobic surfactant proteins in the developing fetal lung. Removal from the diabetic environment results in an apparent return to normal levels of expression.