Effects of prenatal administration of vitamin A on late fetal lung development and expression of Hoxa5 in experimental congenital diaphragmatic hernia

Abstract

Objective To explore the effects of prenatal administration of vitamin A(VitA) on late fetal lung development and expression of Hoxa5 and elucidate the possible mechanism of pulmonary maturation in a rat model of congenital diaphragmatic hernia(CDH). Methods A total of 12 pregnant rats were randomly divided into CDH, CDH+ VitA and control groups. CDH was induced in pregnant rats after administration of 100 mg nitrofen at E9.5(day 9.5 of gestation, term in 22 days). Nitrofen-induced CDH+ VitA group received VitA(15 000 IU dissolved in 1 ml oil) i. g. at E10.5. Pregnant rats without nitrofen were selected as control group. Fetal lungs were collected at E21.5. Histological pulmonary development was analyzed by hematoxylin & eosin staining. The expressions of Hoxa5 mRNA and protein were detected by real-time quantitative polymerase chain reaction(qRT-PCR) and Western blot respectively. Results The rate of CDH decreased markedly after prenatal VitA(CDH group 50.0% vs CDH+ VitA group 28.3%). The areas of alveolar space of CDH, control and CDH+ VitA groups were(332.83±72.19),(1 443.37±285.94)and(907.07±54.78) μm2; thickness of alveolar septum(9.72±2.18),(6.17±1.54) and(7.26±1.52)μm; number of pulmonary artery 3.68±1.03, 7.20±0.91 and 6.24±0.88; luminal area to total transectional area(15.76±4.87)%,(38.74±4.94)% and(30.18±7.03)% respectively. Histological finding showed that antenatal administration of VitA promoted lung maturity in CDH+ VitA group. The expression of Hoxa5 significantly decreased in CDH+ VitA group versus CDH group. Conclusions Prenatal administration of VitA promotes pulmonary maturation in nitrofen-induced CDH and down-regulates the expression of Hoxa5. And the improvement of pulmonary hypoplasia may be regulated by the expression of Hoxa5. Key words: Hernia, diaphragmatic; Lung; Vitamin A