A healthy pregnancy is crucial for a healthy baby and a healthy start to life. Preeclampsia is a pregnancy-induced disorder unique to humans and a major cause of maternal and perinatal morbidity and mortality worldwide. Preeclampsia is a complex multi-system disease, diagnosed by sudden onset hypertension (>20 weeks gestation) and at least one other associated complication including proteinuria, placental or maternal organ dysfunction. Preeclampsia’s impact extends beyond pregnancy: preeclampsia has significant long-term health consequences for both the mother and child including elevated risk of developing chronic kidney and cardiovascular disease.
Poor implantation and placentation in the first trimester of pregnancy are widely accepted to be the sentinel causes of pregnancy diseases including preeclampsia. Despite decades of research advances in the detection, prevention and treatment of preeclampsia, particularly term preeclampsia, have been limited by our inadequate understanding of its pathogenesis. Chorionic villus samples (CVS) are placental biopsies collected between 11-13 weeks gestation. These biopsies represent a unique opportunity to understand the early pregnancy placental dysfunction present in pregnancies that subsequently develop preeclampsia.
In a world-first, we have performed multiple omics analyses on CVS from pregnancies that developed preterm (<37 weeks) and term (>37 weeks gestation) preeclampsia as well as normotensive, uncomplicated pregnancies: ‘bulk’ (whole tissue) RNA sequencing (mRNA, short RNA) and quantitative label free proteomics as well as spatial transcriptomics. Using this innovative approach we have identified for the very first time an ‘early pregnancy placental molecular signature’ in placentas that subsequently develop preeclampsia. This study provides crucial insight into the early pregnancy placental dysfunction that precedes preeclampsia.