Intrauterine growth restriction transiently delays alveolar formation and disrupts retinoic acid receptor expression in the lung of female rat pups

BACKGROUND: We showed that intrauterine growth restriction (IUGR) increases distal airspace wall thickness at birth (postnatal age 0; PO) in rat pups (saccular stage of lung development). However, that report did not assess whether the saccular phenotype persisted postnatally or occurred in males or females, nor did the report identify a potential molecular pathway for the saccular phenotype at PO. We hypothesized that IUGR persistently delays alveolar formation and disrupts retinoic acid receptor (RAR) mRNA and protein levels in the lung of rat pups in a postnatal age- and sex-specific manner. METHODS: IUGR was induced in pregnant rats by bilateral uterine artery ligation. Alveolar formation and expression of RAR alpha, -beta, and -gamma were quantified at P0, P6 (alveolar stage), and P21 (postalveolarization). RESULTS: IUGR increased distal airspace wall thickness in female pups at PO only. IUGR did not affect male pups at any age. IUGR transiently increased lung RAR-beta protein abundance, which inhibits alveolar formation, at PO in female pups. Serum retinol concentration was normal at all ages. CONCLUSION: IUGR alone is not sufficient to persistently delay postnatal alveolar formation or disrupt expression of RARs. We speculate that for IUGR to delay alveolar formation postnatally, a second insult is necessary.