Oral Presentation 6th Australian Health and Medical Research Congress 2012

Placental imprinted genes and environmental factors that affect epigenetic state (#16)

Claire T Roberts 1 , Sam Buckberry 1 , Tina Bianco-Miotto 1 , Stefan Hiendleder 1
  1. Robinson Institute, University of Adelaide, Adelaide, Australia

The placenta is the key mediator of nutrient, gaseous and waste exchange between the maternal and fetal circulations. It also orchestrates much of how the mother adapts to pregnancy by secreting a profusion of growth factors and hormones into the maternal circulation. Concomitantly, placental differentiation and function are influenced by maternal genetics, nutrition and various environmental exposures. These have the potential to modify dynamic flux of epigenetic state in both placenta and fetus and program health in pregnancy and beyond. Altered genetic imprinting has been implicated in pregnancy complications in which defective early placentation plays an important role. We recruited healthy women to the SCOPE study in Adelaide and Auckland. We recorded clinical and environmental data such as maternal BMI, smoking, socioeconomic index, diet, circulating vitamin D and folate, as well as pregnancy outcome. We collected placentas from a sub-set of women at delivery. We also obtained first trimester placenta samples from elective pregnancy terminations. We are investigating changes in epigenetic state across gestation by studying imprinted gene expression and DNA methylation. To do this, we have isolated DNA and RNA from first trimester and term placentas and used pyrosequencing to quantify allele-specific gene expression and DNA methylation. For the reciprocally imprinted H19 and IGF2 genes, we have shown complete imprinting for IGF2 by 6 weeks gestation but allele-specific expression from the paternally repressed H19 allele was variable across first trimester. Site-specific methylation levels in the H19 promoter and upstream transcription factor binding sites showed several differentially methylated regions between first trimester and term, although only methylation in one region was correlated with H19 allelic expression. Our research demonstrates imprinting plasticity in a genomic region featuring genes that significantly influence placental development. Differences in environmental exposures and in pregnancy complication rates between the Adelaide and Auckland cohorts provide clues to identify factors that may alter epigenetic state and negatively impact on placental development.