516: Global transcriptomic analysis of sibling placentas in twin gestations complicated by preeclampsia

Abstract

Preeclampsia (PE) is a disease of incompletely understood etiology that is the leading contributor to iatrogenic preterm birth (PTB). Our objective was to identify if PE in dichorionic pregnancies is characterized by similarities or dissimilarities in the transcriptome profile of the two placentas. Total RNA was extracted from 60 placental villous tissue samples and subjected to RNA-seq using the Illumina platform. Our study was designed to include two analytical stages: In the first stage placental samples (n=18) originated from singleton pregnancies with unambiguous clinical phenotypes: 1) severe features early-onset PE (sPE, n=8, GA: 30±1 wks); 2) idiopathic preterm birth (n=5, GA: 32±1wks) and 3) term non-labor (n=5, GA: 39±1wks). These samples were used to extract a generic transcriptomic signature of PE placenta. In the second stage placentas of 16 twin pregnancies classified based on chorionicity and PE diagnosis were included as follows: di-di nonPE (n=7, GA: 32±1 wks), mono-di nonPE (n=2, GA: 32±1 wks), di-di PE (n=5, GA: 33±2 wks) and mono-di PE (n=2, GA: 33±3 wks). Two separate biopsies were sequenced from monochorionic placentas. An additional set of singleton PE placentas (n=10, GA: 33±1 wks) was sequenced interspaced among the twin placentas to control for batch effects. Principal components analysis (PCA) and statistical modeling for similarity and dissimilarity between sibling placentas were applied. Our first stage analysis extracted a subset of 613 transcripts differentially expressed between sPE and non-PE singleton placentas. This molecular classifier showed linear separability among first stage samples independent of GA at birth. When applied to twin gestation placentas the classifier revealed several characteristics: 1) In the non-PE cases, biopsies from monochorionic placentas had more similar expression patterns of the genes composing the PE signature than dichorionic placentas which were more scattered in the PCA space (Fig. A); 2) Monochorionic nonPE placentas have closer proximity to the PE space compared to singleton nonPE placentas; 3) Dichorionic sibling placentas of pregnancies complicated by PE were the most discordant (Fig. B). In dichorionic pregnancies complicated by PE, the disease affects each placenta individually. Conversely, PE in twins could be the result of a single diseased placenta.