The role of imprinting in placentation and obstetrical complications

Up to one per cent of pregnancies in British Columbia end in stillbirth. Two conditions thought to contribute to the rate of stillbirths are pre-eclampsia and intrauterine growth restriction (IUGR). Pre-eclampsia – a form of pregnancy-induced high blood pressure – affects approximately five per cent of pregnancies, and can be life-threatening to both mother and fetus. IUGR – where the fetus is significantly undersized for its gestational age – also affects approximately five per cent of pregnancies, and is linked to health problems at birth and beyond. Abnormal placental development is thought to be responsible for many complications of pregnancy, including pre-eclampsia and IUGR. The causes underlying abnormal placental development are largely unknown. It may involve errors in DNA methylation, a mechanism used to regulate the activity of certain genes - particularly imprinted genes. Unlike the more common type of genetic inheritance where the outcome in the offspring will depend on whether a gene is dominant or recessive, imprinted genes are parent-of-origin-specific, meaning they are only expressed from either the maternal or paternal chromosome. The placenta has an overabundance of genes expressed in this way. Errors in DNA methylation and imprinting can result in changes in gene expression. Danielle Bourque’s project aims to determine if disruption of normal DNA methylation and imprinted gene expression leads to the abnormal placental development associated with pre-eclampsia or IUGR. The eventual goal is to develop a strategy to improve early diagnosis of pre-eclampsia and IUGR, which will lead to improved treatments and outcomes for both mother and baby.