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Tracheal occlusion (TO) accelerates fetal lung growth but this may be at the expense of maturation indicators. Maternal betamethasone (BM) administration enhances lung maturation. We investigated the effects of both antenatal interventions combined, in terms of proliferation and maturation on a transcriptional level in the saccular phase, using the nitrofen rat model for congenital diaphragmatic hernia (CDH).
Nitrofen was gavage fed to 23 Wistar rats to induce fetal CDH (ED9.5; term=22d). Fetuses underwent TO (n=27) or no fetal surgery (C;n=31) at ED19 (pseudoglandular phase). BM (0.2 mg/kg, SC) or saline (S) was administered to the mother on ED20 (canalicular phase). Fetuses were harvested at ED21.5 (saccular phase) to assess lung-to-body-weight ratio (LBWR) and gene expression levels (n=24) of Ki67 (proliferation), surfactant B (SPB; maturation) and elastin (elasticity), normalized to GAPDH by quantitative RT-PCR, in CDH fetuses. Means and least square means (LSM) were compared by ANOVA and unpaired t-tests at p<0.05.
The increase in LBWR by TO (LSM:p<0.001) was not less in BM exposed fetuses. Ki67 was increased by TO (LSM:p=0.004) but decreased by BM (LSM:p<0.0001), whilst SPB was decreased by TO (LSM:p=0.01) but increased by BM (LSM:p=0.007). Elastin was increased by BM (LSM:p=0.006) but not by TO (LSM:p=0.098). Following TO+BM, proliferation was inhibited as compared to TO+S (p=0.0001), with recovery of SPB (p=0.84) and increased elastin content (p=0.003) as compared to saline controls.
Maternal BM causes recovery of SPB and elastin, which is decreased after TO, at the expense of a decrease in proliferation.