Endometrial decidualization is critical for pregnancy establishment and maintenance. This process promotes endometrial remodeling allowing placental cytotrophoblasts (CTBs) invasion up to an appropriate depth to form the maternal-fetal interface. A shallow CTBs invasion compromises healthy pregnancy and it is associated with the development of severe preeclampsia (sPE). Our working hypothesis is that defective decidualization impairs the adaptation of the maternal “soil” ─the decidua─ to be invaded by CTBs and plays a pivotal role in the etiology of sPE. Previously, we have demonstrated the existence of an in vitro defective decidualization of endometrial stromal cells isolated from women who suffered sPE. The present thesis doctoral aims to dilucidated the existence of a in vivo footprint and the molecular mechanisms encoding endometrial defective decidualization that might identify the maternal contribution to sPE. To that purpose global RNA sequencing was applied to obtain the transcriptomic profile of endometrium collected from non-pregnant women who suffered sPE (n=24) in a previous pregnancy versus women who did not develop this condition (n=16). Samples were randomized in two cohorts, the training set to identify the fingerprint encoding defective decidualization in sPE and the test set for its subsequent validation. Transcriptional analysis revealed 593 differentially expressed genes in sPE compared to controls. From those, 120 (≥1.4-fold; FDR<0.05) genes were selected to formulate the footprint encoding defective decidualization. This signature allowed us to effectively segregate samples into sPE and control groups in both cohorts, the training and the test set. Gene Ontology enrichment and an interaction network were performed to deeper in pathways impaired by genetic dysregulation in sPE. Major biological processes affected were associated with decidualization and sPE pathogenesis such as extracellular matrix and immune response. High-level pathways were also identified using the Kyoto Encyclopedia of Genes and Genomes, revealing enriched pathways involved in response to pathogens including coronavirus disease. This result suggests the immune system is dysregulated in sPE patients. Then, since decidualization is tightly regulated by progesterone and estrogen, we assessed the link between this hormonal signaling and the gene expression imbalance encoding defective decidualization. We identified the footprint was composed by 94 genes highly expressed in the endometrium of which 47.9% are modulated by estrogen receptor 1 (ER1) and 45.7% by progesterone receptor (PR). An interactome network confirmed these receptors were strongly interconnected with the proteins codified by the genes encoding defective decidualization. Moreover, gene expression and protein abundance of ER1 and PR was significantly downregulated in sPE. Specifically, the PR isoform B was impaired in sPE, while the isoform A was not affected. Furthermore, STAT3 and PLZF, critical mediators of PR signaling, were upregulated in the group of cases. Our data support the concept that in vivo defective decidualization is responsible, at least in part, for the maternal contribution to sPE. Further, we postulate that impaired ER1 and PR-B are potential drivers of compromised decidualization, including dysregulation of endothelial and immune response observed in sPE. These findings open new horizons in the search for early detection, prevention, and therapy strategies since the origin of sPE could lie in maternal endometrial health.