title: Intrafetal glucose infusion alters glucocorticoid signaling and reduces surfactant protein mRNA expression in the lung of the late-gestation sheep fetus.
abstract: Increased circulating fetal glucose and insulin concentrations are potential inhibitors of fetal lung maturation and may contribute to the pathogenesis of respiratory distress syndrome (RDS) in infants of diabetic mothers. In this study, we examined the effect of intrafetal glucose infusion on mRNA expression of glucose transporters, insulin-like growth factor signaling, glucocorticoid regulatory genes, and surfactant proteins in the lung of the late-gestation sheep fetus. The numerical density of the cells responsible for producing surfactant was determined using immunohistochemistry. Glucose infusion for 10 days did not affect mRNA expression of glucose transporters or IGFs but did decrease IGF-1R expression. There was reduced mRNA expression of the glucocorticoid-converting enzyme HSD11B-1 and the glucocorticoid receptor, potentially reducing glucocorticoid responsiveness in the fetal lung. Furthermore, surfactant protein (SFTP) mRNA expression was reduced in the lung following glucose infusion, while the number of SFTP-B-positive cells remained unchanged. These findings suggest the presence of a glucocorticoid-mediated mechanism regulating delayed maturation of the surfactant system in the sheep fetus following glucose infusion and provide evidence for the link between abnormal glycemic control during pregnancy and the increased risk of RDS in infants of uncontrolled diabetic mothers.
authors.affiliation: Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia; and Molecular and Evolutionary Physiology of the Lung Laboratory, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Erin V
authors.initials: EV
authors.lastname: McGillick
authors.affiliation: Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia; and.
authors.forename: Janna L
authors.initials: JL
authors.lastname: Morrison
authors.affiliation: Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia; and.
authors.forename: I Caroline
authors.initials: IC
authors.lastname: McMillen
authors.affiliation: Molecular and Evolutionary Physiology of the Lung Laboratory, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia sandra.orgeig@unisa.edu.au.
authors.forename: Sandra
authors.initials: S
authors.lastname: Orgeig
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D000818:Animals; D001784:Blood Gas Analysis; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D023421:Models, Animal; D011247:Pregnancy; D011270:Pregnancy, Animal; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012756:Sheep / Q000196:embryology / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D007328:Insulin; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D017526:Receptor, IGF Type 1; D005947:Glucose
keywords: diabetes; glucose; obesity; surfactant