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Failure to Detect a Stimulatory Effect of Estradiol-17β on Ovine Fetal Lung Maturation

ABSTRACT. It has been reported that estradiol-17β (E2) stimulates rat and rabbit fetal lung maturation; however, E2 was not directly administered to the fetus in these experiments. Therefore, we used the chronically instrumented fetal sheep to study the effects of 14 days of continuous E2 infusion on fetal lung maturation. Animals were instrumented on days 104-106 of gestation, then infused with either saline or E2 (100 μg/day) from 111 to 127 days of gestation. Fetal plasma concentrations of E2, estrone, and cortisol, and tracheal fluid phosphatidylcholine:sphingomyelin ratios and phosphatidylcholine flux were measured daily in E2-infused (n = 8) and salineinfused (n = 6) control animals. At 127 days of gestation, fetuses were sacrificed and lung tissue samples obtained for biochemical and morphological analyses. Plasma E2 levels rose from 0.045 ± 0.001 (x ± SE) to 7.45 ± 5.31 ng/ml (p < 0.05) in E2-infused animals whereas levels remained<0.06 ng/ml in saline-infused animals. Plasma estrone concentrations also were significantly elevated by E2 infusion. Plasma contisol concentrations increased from 0.58 ± 0.08 to 0.88 ± 0.40 μg/dl in E2-treated fetuses during the last week of infusion whereas values in control animals were unchanged. The ratio of acetone-precipitated phosphatidylcholine to sphingomyelin and the flux of acetone-precipitated phosphatidylcholine in tracheal fluid were not affected by E2 infusion. Fetal lung tissue phospholipid content was also unaffected by E2 infusion. Furthermore, there was no consistent effect of E2 infusion on the histological structure of the fetal lung tissue as determined by morphometric methods. Therefore, we conclude that prolonged elevations in plasma E2 in the early to middle 3rd trimester of gestation, i.e., prior to 128 days of gestation, do not stimulate lung maturation in the intact ovine fetus.