ABSTRACT
BACKGROUND: Maternal tobacco smoke (MTS) predisposes human and rat offspring to visceral obesity in early adulthood. Glucocorticoid excess also causes visceral obesity. We hypothesized that in utero MTS would increase visceral adiposity and alter the glucocorticoid pathway in young adult rats. METHODS: We developed a novel model of in utero MTS exposure in pregnant rats by exposing them to cigarette smoke from E11.5 to term. Neonatal rats were cross-fostered to control dams and weaned to standard rat chow through young adulthood (postnatal day 60). RESULTS: We demonstrated increased visceral adiposity (193%)*, increased visceral adipose 11-ß hydroxysteroid dehydrogenase 1 mRNA (204%)*, increased serum corticosterone (147%)*, and no change in glucocorticoid receptor protein in adult male MTS rat offspring. Female rats exposed to MTS in utero demonstrated no change in visceral or subcutaneous adiposity, decreased serum corticosterone (60%)*, and decreased adipose glucocorticoid receptor protein (66%)*. *P < 0.05. CONCLUSION: We conclude that in utero MTS exposure increased visceral adiposity and altered in the glucocorticoid pathway in a sex-specific manner. We speculate that in utero MTS exposure programs adipose dysfunction in adult male rat offspring via alteration in the glucocorticoid pathway.
Subject(s)
Adipocytes/drug effects , Corticosterone/blood , Intra-Abdominal Fat/drug effects , Nicotiana/adverse effects , Prenatal Exposure Delayed Effects/pathology , Smoking/adverse effects , 11-beta-Hydroxysteroid Dehydrogenases/metabolism , Adipokines/blood , Adiposity , Animals , Cotinine/blood , Female , Glucocorticoids , Inflammation/pathology , Male , Pregnancy , Prenatal Exposure Delayed Effects/blood , Rats , Receptors, Glucocorticoid/metabolism , Smoke/adverse effects , Time FactorsABSTRACT
BACKGROUND: We showed that intrauterine growth restriction (IUGR) increases distal airspace wall thickness at birth (postnatal age 0; P0) 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 P0. 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 RARα, -ß, and -γ were quantified at P0, P6 (alveolar stage), and P21 (postalveolarization). RESULTS: IUGR increased distal airspace wall thickness in female pups at P0 only. IUGR did not affect male pups at any age. IUGR transiently increased lung RAR-ß protein abundance, which inhibits alveolar formation, at P0 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.
