Disrupted PGR-­B and ESR1 signaling underlies defective decidualization linked to severe preeclampsia

In the present study, we aimed to discern the preconception decidual transcriptomic signature associated with in vivo defective decidualization in women who suffered sPE in a previous pregnancy. First, we performed a comparative global transcriptional profiling of endometrium from women who developed sPE in a previous pregnancy and from women who never have had sPE. Then, we selected those genes that were significantly deregulated 1.4-fold higher (FDR<0.05) and have an EntrezID code. As a result, we formulate a transcriptional signature associated with defective decidualization composed by 120 genes. Overall design: A total of 40 non-pregnant women who experienced a previous pregnancy were enrolled in this study for endometrial RNA-sequencing analysis. Endometrial samples were obtained during late secretory phase in 24 women who had developed sPE in a previous pregnancy and in 16 women with no history of sPE with full term (n=8) and preterm pregnancies (n=8) as controls. The experimental design was based on a stratified random sampling with a 70:30 proportion in two cohorts: a training and validation set of samples. The training set of samples was analyzed by RNA-seq to identify the global transcriptomic profiling changes between control (n=12) and sPE (n=17) samples. Finally, targeted analysis of the transcriptional signature was validated in the test set composed of controls (n=4) and sPE (n=7).