Maternal Hyperglycemia Modifies Extracellular Matrix Signaling Pathways in Neonatal Rat Lung

Abstract

Background: Maternal diabetes is associated with numerous adverse effects in fetal and neonatal organs, including the lungs. Objective: To investigate the effects of intrauterine hyperglycemia on neonatal lung biological signaling, we performed a microarray analysis in the lungs of four 14-day-old rat pups born to a hyperglycemic dam and in four age mate control pup lungs. Methods: Total RNA was isolated and cDNA was hybridized to the Illumina Sentrix® RatRef-12 BeadChip. A total of 22,000 genes were analyzed for expression profiles and functional gene clustering. Ten selected genes differentially expressed in microarray were additionally analyzed by the real-time polymerase chain reaction. Results: Two hundred twenty-seven genes were differentially expressed in neonatal rat lungs exposed to intrauterine hyperglycemia when compared to normoglycemic controls (fold change > 1.2, p < 0.001). Functional clustering analysis revealed increased expression in signaling pathways involved with extracellular matrix regulation. The most significantly downregulated functions were cell proliferation, extracellular region, cell adhesion and reactive oxygen species metabolism. Conclusion: We found significant hyperglycemia-induced gene expression alterations in neonatal rat pulmonary tissue which may interfere with lung growth and biological signaling pathways.

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats

“…Both glucose and lipid metabolic substrates transferred in excess from maternal circulation into the fetuses have been involved in the generation of a proinflammatory environment that challenges the development of the fetal organs (Herrera & Ortega-Senovilla 2010, Lappas et al 2011. In the fetal lung, the effect of maternal diabetes is evidenced by structural alterations (Koskinen et al 2012), delayed pulmonary maturation (Piper 2002), altered production of surfactant proteins and lipids (Bourbon & Farrell 1985, Trevino-Alanis et al 2009, and increased pro-oxidative and proinflammatory pathways (Koskinen et al 2010, Kurtz et al 2012, Milla & Zirbes 2012.…”

Elevated Acetoacetate and Monocyte Chemotactic Protein-1 Levels in Cord Blood of Infants of Diabetic Mothers

“…This may result in birth defects, spontaneous abortions, macrosomia, asphyxia, respiratory distress syndrome and other metabolic complications [1-3]. Infants of diabetic mothers may be at an increased risk for developing diabetes and/or obesity later in life [1].…”

Delay in rat lung alveolarization after the combined exposure of maternal hyperglycemia and postnatal hyperoxia

“…Perturbations of these processes may originate already prenatally and compromise the pulmonary tolerance to additional postnatal insults. We have previously shown that fetal exposure to hyperglycemia leads to multiple aberrations in gene signaling pathways directing the functional, biochemical, and morphological maturation of the neonatal rat lung . Further, maternal hyperglycemia was followed by thinning of alveolar septa in association with increased apoptosis and proliferation during the first postnatal week in neonatal lungs implicating induced structural remodelling .…”