Perturbed neonatal size is associated with differential DNA methylation and gene expression in human placentas

Fetal growth in utero is affected by both inherent genetic programming in combination with environmental factors, such as maternal health and nutrition. Epidemiologic data in growth-altered fetuses, either growth-restricted (IUGR) or large for gestational age (LGA), demonstrate compelling evidence that these fetuses are at increased risk for cardiovascular and metabolic disease in adulthood. In this study, we used RRBS to examine genome wide DNA methylation variation in placental samples from offspring born IUGR, LGA, and appropriate for gestational age (AGA). We identified almost 200 differentially methylated genes among these groups. Among these genes, the differentially methylated regions were disproportionately located in transcription-regulatory regions such as promoters. Our results suggest that the gene expression and methylation state of the human placenta are related and sensitive to the intrauterine environment. We profiled DNA methylation for 17 human placentas, in which 5 were from LGA, 6 from IUGR and 6 from AGA placentas as controls