Circulating RNA coding genes regulating apoptosis in maternal blood in severe early onset fetal growth restriction and pre-eclampsia

Abstract

To determine whether the intrinsic apoptosis pathway is differentially expressed in placenta and maternal blood in severe preterm fetal growth restriction (FGR) and pre-eclampsia (PE), and to examine whether circulating RNA in maternal blood may be potential biomarkers. Maternal blood samples and placental biopsies were collected from women with preterm: FGR (n=20), PE without FGR (n=8) and controls (n=20). Real-time PCR examined the expression of genes in the intrinsic apoptosis pathway in FGR and PE, stratified according to the severity of placental insufficiency. Severe preterm FGR, with or without PE, was associated with increased expression of BCL2, BCL-XL, BIM, BAD and Survivin in both the placenta and maternal blood (1.6 to 3.3-fold, P<0.05). In preterm PE, but not FGR, there was increased placental expression of BCL-XL and BCL2 (1.6 to 2.5-fold, P<0.05), but only BCL2 was significantly increased in the maternal blood (1.8-fold, P<0.05). Increased expression of genes of the intrinsic apoptosis pathway reflected the severity of FGR as determined by deteriorations in umbilical artery Doppler velocimetry. In severe early onset FGR there was increased expression of genes regulating intrinsic apoptosis in both the placenta and maternal blood. Circulating RNA regulating placenta apoptosis may be used to develop noninvasive novel biomarkers for FGR.