Placental gene expression is related to glucose metabolism and fetal cord blood levels of insulin and insulin-like growth factors in intrauterine growth restriction

Abstract

Despite the importance of glucose for fetal growth, placental gene expression related to the glycolytic pathway has not been studied. Insulin-like growth factors (IGFs) and insulin are known to play a critical role in fetal growth. In our study, we identified differentially expressed genes related to the glycolytic pathway using oligonucleotide microarray analysis and confirmed these genes with quantitative real-time PCR between uncomplicated pregnancies and pregnancies with intrauterine growth restriction (IUGR). We also compared the concentrations of insulin and IGFs in cord blood between the two groups. Microarray experiments identified increased expression of glycolytic enzyme-related genes, including lactate dehydrogenase C (LDHC), dihydrolipoamide S-acetyltransferase (DLAT), 6 phosphofructo-2-kinase/fructose-2, 6-biphosphatase 2 (PFKFB2), oxoglutarate dehydrogenase, phosphorylase, and insulin-like growth factor (IGF)-II and decreased expression of IGF-I in placentas from pregnancies with IUGR (p<0.05). There were significantly lower concentrations of glucose, insulin, IGF-1, and IGF-II in the fetal cord blood of pregnancies with IUGR (p<0.05). Microarray analysis revealed increased expression of enzyme genes related to the tricarboxylic acid cycle pathway in placentas from pregnancies with IUGR; the cause of hypoglycaemia in IUGR is attributed to increased glycolytic pathway activity in placentas from pregnancies with IUGR.