P-516 Defective decidualization secretome in severe preeclampsia

Abstract Study question How defective decidualization (DD) induces a differential secretome compromising embryo invasion in severe preeclampsia (sPE). Summary answer DD endometrial stromal cells isolated from sPE patients secrete a differential secretome in response to hormonal stimuli. What is known already Endometrial decidualization is a primary driver of embryo invasion and placentation. This process is highly coordinated by estradiol and progesterone, which transform the endometrial stromal cells (ESCs) into decidualized cells specialized in the secretion of specific molecules. The secretome of ESCs regulates the endometrial differentiation into the decidua, including immune system and endothelial function regulation. Previously, we have demonstrated the existence of in vitro and in vivo defective decidualization (DD) in women who suffered sPE due to an impaired response to hormonal stimuli. However, the molecular mechanism that connects DD with a hostile maternal environment for embryo invasion remains unexplored. Study design, size, duration Human ESCs from women who suffered sPE (n = 3) and women with normal pregnancies as controls (n = 3) were isolated from endometrial biopsies collected at the time of late-secretory phase. ESCs were cultured using an established in vitro decidualization model, including three technical replicates per sample and condition. Culture media (n = 36) were analysed by mass spectrometry to characterize their global secretome, unveiling the differential secreted factors in DD underlaying sPE. The study duration was 12 months. Participants/materials, setting, methods For in vitro decidualization, isolated human ESCs were cultured for three days in the absence or presence of hormonal stimuli (0.5mM cAMP + 1μM MPA) in serum-free media. Culture media from decidualized and non-decidualized conditions were collected to analyse the secreted proteins by high-resolution mass spectrometry-based proteomics. Protein quantification was performed in the MaxQuant and Perseus software. This approach enables the characterization of the global secretory program as well as the discovery of proteins. Main results and the role of chance We identified and quantified a total of 1.117 proteins secreted by ESCs. In the transition from non-decidualized to decidualized status, the secretome of the control group showed significant differences in the abundance of 83 proteins (p-value