The molecular role of PCBP2 and Elabela in pregnancy From translational inhibition to human disease

This thesis focusses on the contribution of PCBP2 and ELA (Elabela) in placentation and extravillous trophoblasts (EVTs) differentiation and the further investigation of the spatiotemporal regulation of the latter during the progressed stages of pregnancy that includes the development of the embryo. In chapter 1 I provide a short background on preeclampsia and HELLP syndrome and outline the existing knowledge on the involvement of the apelinergic axis and its components ELA and Apelin in preeclampsia, and the RNA splicing proteins, PCBP1, PCBP2 and YBX1 in the HELLP syndrome. Chapter 2 includes a systematic review of the studies on the pathophysiological role of Apelin, ELA and their common receptor APJ in human pregnancies in relation to preeclampsia. In chapter 3, I outline the proper use of the commercially available ELISA kit for ELA detection in human plasma that will minimize discrepancies between studies of different groups. In chapter 4, I investigate the role ELA in the regulation of differentiation of human EVTs. Additionally, by analysing data from three different cohorts of healthy and preeclamptic pregnancies, I assess the circulation levels of ELA and its expression in healthy and preeclamptic placental tissue. In chapter 5, a study in progress, I identify the possible elements involved in the translational inhibition of ELA in embryonic development of vertebrates. In chapter 6, I further investigate the role of the RNA splicing proteins YBX1, PCBP1, and PCBP2, originally picked up through their binding to a non-coding RNA identified by genome-wide linkage analysis in HELLP syndrome patients, in the regulation of EVT invasion during first trimester placenta development. Finally, in chapter 7 I discuss the findings of this thesis and evaluate possible future implications.