Ontogeny and nutritional programming of uncoupling protein-2 and glucocorticoid receptor mRNA in the ovine lung

This study investigated the developmental and nutritional programming of uncoupling protein-2 (UCP2), glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) mRNA in the sheep lung from the time of uterine attachment to 6 months of age. The effect of maternal nutrient restriction on lung development was determined in early to mid gestation (i.e. 28-80 days gestation, period of maximal placental growth, and embryonic and pseudoglandular stages of fetal lung development) and late gestation (i.e. 110-147 days gestation, period of maximal fetal growth, and canalicular and saccular stages of fetal lung development). Fetal lungs were sampled at 80 and 140 days (term approximately 148 days) gestation, and sheep lungs at 1, 7, 30 days and 6 months. GR and 11betaHSD1 mRNA were maximal at 140 days gestation, whereas UCP2 mRNA peaked at 1 day of age and then declined with postnatal age. Maternal nutrient restriction in both early-to-mid and late gestation had no effect on lung weight, but increased UCP2, GR and 11betaHSD1 mRNA abundance at every sampling age. These findings suggest that the developmental ontogeny of UCP2 mRNA in the ovine lung is under local glucocorticoid hormone action and that maternal nutrient restriction has long-term consequences for UCP2 and GR mRNA abundance in the lung irrespective of its timing.