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- W4387396555 abstract "Defective decidualization (DD) of the human endometrium has been associated to reproductive pathologies such as endometriosis or miscarriage of euploid embryos as well as pregnancy complications as severe preeclampsia (sPE). Here, we aim to unveil the global proteome profile underlaying DD of endometrial stromal cells (ESCs) isolated from women who suffered sPE in their previous pregnancy. Endometrial biopsies were collected in the late-secretory phase from women with a previous sPE pregnancy (n=7) and controls with normal pregnancies (n=6). ESCs were isolated and decidualized in vitro using an established protocol (0.5 mM cAMP + 1 μM MPA) in serum-free media during five days. Three technical replicates per sample and condition were included. Cells were lysate and processed for the analysis of intracellular proteins by a single-run liquid chromatography mass spectrometry (LC-MS/MS). Protein quantification was performed using MaxQuant and Perseus software. Immunostaining was performed to validate major findings. A total of 3,947 intracellular proteins were identified in this analysis. The global proteome revealed that ESCs with DD isolated from sPE patients present a differential proteome profile compared controls. The DD group showed significant changes in 272 proteins (FDR < 0.05) and the control group showed significant changes in 263 proteins (FDR < 0.05). The overlapping of the two datasets revealed a common proteome of 133 proteins (∼48%); whereas 52% of proteins composing the global proteome during the decidualization reprogramming was specific for each group. Proteins shared by the two groups (n=133) were involved in biological processes of decidualization such as extracellular matrix, cell migration and tissue remodelling. The proteins specific of controls (n=130) were also involved in pathways of decidualization biology, while the proteins specific of sPE (n=139) revealed an enrichment for pathways involved in response to viral infections such as entry into host cell. Notably, ESCs from sPE show upregulated proteins involved in inflammasomes inhibition. Inflammasomes are a complex of proteins that induce immune responses to pathogens, and they have been associated with placental inflammation in sPE pregnancies. We assessed two classical markers of inflammasomes (ASC and IL-1B) in vivo by immunofluorescence, corroborating the downregulation in DD. ESCs isolated from sPE patients show an abnormal proteome profile in response to hormonal stimuli leading to DD. This proteomic footprint includes proteins involved in altered decidualization pathways, but also proteins involved in response to viral infections. Further, our data evidence an alteration of inflammasome machinery during DD in sPE." @default.
- W4387396555 created "2023-10-07" @default.
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- W4387396555 date "2023-10-01" @default.
- W4387396555 modified "2023-10-07" @default.
- W4387396555 title "GLOBAL PROTEOME PROFILE OF DEFECTIVE DECIDUALIZATION" @default.
- W4387396555 doi "https://doi.org/10.1016/j.fertnstert.2023.08.417" @default.
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