Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations

Abstract

BACKGROUND:The maternal signs of preeclampsia, which include the new onset of high blood pressure, can occur because of faulty placentation. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis. OBJECTIVE: Our goal was to enrich syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases. Total RNA was subjected to global transcriptional profiling to identify RNAs that were misexpressed compared with controls. STUDY DESIGN: This was a cross-sectional analysis of placentas from women who had been diagnosed with severe preeclampsia. Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection. Laser microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts. After RNA isolation, a microarray approach was used for global transcriptional profiling. Immunolocalization identified changes in messenger RNA expression that carried over to the protein level. Differential expression of noneprotein-coding RNAs was confirmed by in situ hybridization. A 2-way analysis of variance of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls. Cajal body foci were visualized by coilin immunolocalization. RESULTS: Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly differentially expressed genes. They included molecules that are known to be expressed by each subpopulation, which is evidence that the method worked. Genes that were expressed differentially between the 2 groups, in a cell-typeespecific manner, encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy

Loss of placental growth factor ameliorates maternal hypertension and preeclampsia in mice

“…Furthermore, PlGF is a pleiotropic factor implicated in blood pressure regulation via the renin-angiotensin-aldosterone system (67,68). This interaction was beyond the scope of our study, but may be relevant to the pathogenesis of preeclampsia (39,(69)(70)(71)(72). Finally, the impact of local angiogenic factors, particularly VEGF, is an area of interest for future studies, as there is evidence that local regulation of angiogenic factors at the maternal-fetal interface is important for the maintenance of vascular integrity in the placenta (73).…”

Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology

“…Given the functions of defensins, we surmised that these genes were up-regulated in nPTB rather than down-regulated in sPE. The up-regulation of a select natural antimicrobial agent in the nPTB samples is likely attributable to the start of an infectious process that has not yet manifested in terms of the clinical signs (32,33). The low yield of DEGs in this dataset was likely the resul ot the numerous cell types that comprise the DB and the challenges of capturing decidual cells from this complex mixture.…”

Down‐regulated lncRNA AGAP2‐AS1 contributes to pre‐eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype

“…To date, there has been an abundance of evidence that highlights how the aberrant expression of lncRNAs could be involved in various human disorders, including PE . Our previous studies have shown that the down‐regulated expression of TUG1 or HOXA11‐AS could significantly inhibit trophoblasts migration and proliferation and promote cell apoptosis in vitro.…”