Prenatal treatment with retinoic acid promotes pulmonary alveologenesis in the nitrofen model of congenital diaphragmatic hernia

Antenatal use of bosentan and/or sildenafil attenuates pulmonary features in rats with congenital diaphragmatic hernia

“…The final remodeling of the alveolar structures takes place in adult age. [39] This fundamental event of pulmonary development, which is necessary to carry out the gas exchange, is interrupted by CDH.…”

Pulmonary Effects of Prolonged Oligohydramnios following Mid-Trimester Rupture of the Membranes – Antenatal and Postnatal Management

“…They promote alveologenesis and induce alveolar regeneration. Administration of maternal retinoic acid in a nitrofen-induced CDH model promoted lung growth and alveologenesis [52] . The administration of retinoic acid in an 'oligohydramnios-induced' pulmonary hypoplasia rat model, however, did not have a positive effect on pulmonary growth or differentiation [53] .…”

Gene expression analysis in hypoplastic lungs in the nitrofen model of congenital diaphragmatic hernia

“…Observations of diaphragmatic hernia in pups born to dams with vitamin A-deficient diets, which decreased after the administration of vitamin A [8], and studies of retinoid receptor double null-mutant mice, lacking both RARα and β, with diaphragmatic hernias, have led to the hypothesis that abnormalities linked to the retinoid signaling pathway in early gestation may contribute to the etiology of CDH, the retinoid hypothesis [25]. In the nitrofen model, coadministration of large doses of vitamin A reduces the incidence of CDH and attenuates lung hypoplasia [26]. Furthermore, nitrofen has been reported to inhibit retinal dehydrogenase (RALDH-2) [42], the major retinoic acid synthesizing enzyme, whereas other studies have shown a downregulation of Cyp26b1 (a cytochrome P450 that reduces the activity of retinoic acid) and LRAT (lecithinretinol transferase that esterifies retinol to retinyl esters for storage) [27,28].…”

“…An increased expression of matrix metalloproteinase 9 (MMP-9) has been reported [24], as well as an alteration of the retinoid acid pathway at different levels [25][26][27][28]. The lungs of rodents with nitrofen-induced CDH have also been shown to have increased expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 [29], increased angiotensin-converting enzyme activity [30], decreased endothelial isoform of nitric oxide synthase (eNOS) expression [31], increased endothelin-1 and endothelin A vasoconstrictor receptor [32], and altered K + channel expression [33], which might contribute to increased pulmonary vascular tone in the teratogenic model of CDH.…”