Differential placental gene expression in term pregnancies affected by fetal growth restriction and macrosomia.

INTRODUCTION: Extremes of fetal growth are associated with increased perinatal mortality and morbidity and a higher prevalence of cardiovascular disease, obesity and diabetes in later life. We aimed to identify changes in placental gene expression in pregnancies with evidence of growth dysfunction and candidate genes that may be used to identify abnormal patterns of growth prior to delivery.

METHODS: Growth-restricted (n = 4), macrosomic (n = 6) and normal term (n = 5) placentas were selected from a banked series (n = 200) collected immediately after caesarean section. RNA was extracted prior to microarray analysis using Affymetrix HG-U219 arrays to determine variation in gene expression. Genes of interest were confirmed using qRT-PCR.

RESULTS: 338 genes in the growth-restricted and 41 genes in the macrosomic group were identified to be significantly dysregulated (>2-fold change; p < 0.05). CPXM2 and CLDN1 were upregulated and TXNDC5 and LRP2 downregulated in fetal growth restriction. In macrosomia, PHLDB2 and CLDN1 were upregulated and LEP and GCH1 were downregulated.

DISCUSSION: Dysfunctional growth is associated with differential placental gene expression and affects genes with a whole spectrum of developmental and cellular functions. Better elucidation of these pathways may allow the development of biomarkers to identify growth abnormalities and effective prenatal intervention.