Project description:Extreme fetal growth is associated with adult disease through a cellular memory of unknown mechanism. We tested whether heritable epigenetic processes in long-lived CD34+ hematopoietic stem/progenitor cells (HSPCs) showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both extremes of fetal growth are associated with global shifts towards DNA hypermethylation, targeting cis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. A sexually dimorphic response was found, intrauterine growth restriction (IUGR) associated with greater epigenetic dysregulation in males but large for gestational age (LGA) growth affecting females to a greater extent. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular aging characteristics through epigenetic mechanisms, with the potential for identifying infants at higher risk for chronic disease later in life.
