Spontaneous Superimposed Preeclampsia: Chronology and Expression Unveiled by Temporal Transcriptomic Analysis

Preeclampsia (PE), a multifactorial pregnancy-specific syndrome accounting for up to 8% of pregnancy complications, is a leading cause of maternal and fetal morbidity and mortality and PE is also associated with long-term risk of hypertension and stroke for both the mother and fetus. Currently, the only “cure” is delivery of the baby and placenta, largely because the pathogenesis of preeclampsia is not yet fully understood. Preeclampsia is associated with impaired vascular remodeling at the maternal-fetal interface and placental insufficiency; however, the specific factors that contribute to this impairment have not been identified. To identify potential contributing pathways, we examined temporal transcriptomic changes occurring within the uterus, uterine implantation sites, and placentae from the Dahl salt-sensitive (Dahl S) rat model of superimposed preeclampsia compared to Sprague Dawley (SD) rats. We hypothesized that the Dahl S maternal-fetal interface would exhibit a unique temporal transcriptomic profile unveiling novel biomarkers, therapeutic targets, and mechanistic pathways regarding the development of PE. Our initial study focused on evaluation of genes previously linked to the development PE from using real time quantitative PCR (RT qPCR) and total RNA was isolated from uterus (day 0), uterine implantation sites (days 7, 10, 14), and placenta (days 14 and 20). Subsequently, an unbiased transcriptome analysis was performed at each time point using whole genome microarray to identify novel factors involved in PE. 624, 332, 185 , and 366 genes were found to be differentially expressed on days 0, 7, 10 and 14 respectively, with a Reactome Pathway enrichment for “Fatty acid metabolism, Metabolism of water-soluble vitamins and cofactors, Metabolism, Synthesis of substrates in N-glucan biosynthesis on Day 7”; ”Glycerophospholipid biosynthesis, Phospholipid metabolism, and Metabolism of lipids on Day 10”; and “Metabolism of lipids, Phospholipid metabolism, degradation of the extracellular matrix, Fatty acid metabolism, and Collagen degradation on Day 14” in the Dahl S rat vs. SD. Our data revealed numerous pathways that may play a role in the pathophysiology of spontaneous superimposed PE and allow for further investigation of novel therapeutic targets and biomarker development. Whole genome transcript analysis was performed using Affymetrix platform on rat uterine tissue, uterine implantation sites, or placental tissue.