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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Loss of endometrial plasticity in recurrent pregnancy loss (MeDIP-Seq)

ABSTRACT: Decidual transformation of the human endometrium is not dependent on embryo implantation. Instead, this process is initiated during the mid-luteal phase of each cycle in response to the postovulatory rise in progesterone and increasing endometrial cAMP levels. Consequently, decidualization is a reiterative process directly linked to cyclic activation of mesenchymal stem cells (MSCs) and subsequent differentiation into mature stromal cells in regenerating endometrium. We reasoned that aberrant remodeling of the HESC epigenome would disrupt decidualization in RPL patients and account for the functional memory of HESCs in culture. To explore this possibility, we performed MeDIP-seq, which involves immunoprecipitation of DNA with a 5-methylcytosine antibody followed by deep sequencing, on primary HESC cultures established from four RPL patients and four control subjects. Eight samples were analyzed: derived from four control and four recurrent pregnancy loss (RPL) patient cultures.

ORGANISM(S): Homo sapiens

SUBMITTER: Jan Brosens

PROVIDER: E-GEOD-65100 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Loss of endometrial plasticity in recurrent pregnancy loss (MeDIP-Seq)

Project description:Decidual transformation of the human endometrium is not dependent on embryo implantation. Instead, this process is initiated during the mid-luteal phase of each cycle in response to the postovulatory rise in progesterone and increasing endometrial cAMP levels. Consequently, decidualization is a reiterative process directly linked to cyclic activation of mesenchymal stem cells (MSCs) and subsequent differentiation into mature stromal cells in regenerating endometrium. We reasoned that aberrant remodeling of the HESC epigenome would disrupt decidualization in RPL patients and account for the functional memory of HESCs in culture. To explore this possibility, we performed MeDIP-seq, which involves immunoprecipitation of DNA with a 5-methylcytosine antibody followed by deep sequencing, on primary HESC cultures established from four RPL patients and four control subjects.

2015-09-16 | GSE65100 | GEO

Endometrial protein expression and phosphorylation landscape decipher aberrant insulin and mTOR signaling in patients with recurrent pregnancy loss

Project description:Research question: What are the proteomic and phosphoproteomic differences between the endometrium of women with recurrent pregnancy loss (RPL) and healthy control women during the proliferative (P) and secretory (S) phases of the menstrual cycle? Design: The present study collected a total of 54 endometrial samples during either P or S phases from women with RPL (n = 28) or healthy control (n = 26). Comprehensive proteomic and phosphoproteomic analyses were conducted using label-free liquid chromatography-tandem mass spectrometry (n = 44) and verified through western blotting (n = 10). Three comparison groups were established, including the total RPL endometrium compared to the total control (R/C), proliferating endometrium compared to control (RP/CP), and secretory endometrium compared to control (RS/CS). Results: Differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs) were respectively identified in the three comparison groups. Combining pathway enrichment, network analysis, and soft clustering analysis, we identified the insulin/cyclic nucleotide signaling pathway and AMPK/mTOR signaling pathway as the major contributors to the aberration of RPL endometrium. Western blotting verified altered expression of four proteins, including PRKAR1B, ADCY3, PRKAA2, and LPIN2.Conclusions: This exploratory study provides insights into the differentiated protein expression and phosphorylation profiles of RPL endometrium in both P and S phases. The results highlight potential proteins associated with RPL pathogenesis that may serve as potential indicators for RPL. The findings contribute to the identification of potential targets for RPL treatment as well as the pathogenesis of RPL.

2023-10-27 | PXD035234 | Pride

Single-cell sequencing reveals a delicate molecular and cellular interaction during decidualization in humans

Project description:Proper decidualization is a critical determinant of pregnancy success. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure, and miscarriage. However, the mechanism for triggering decidualization of human endometrium is largely unknown. Here we characterized the transcriptomes of four major cells in human endometrium and decidua at single-cell resolution. We discovered the dynamic change characteristics of six major stromal cells. More importantly, a dialogue between IGF1+ stromal cells and IGF1R+ stromal cells initiates endometrial decidualization under regulation of progesterone and estrogen, and IL1B+ stromal cells trigger the apoptosis of epithelial cells and functional remodeling during decidualization. We defined a unique AREG+ NK cell for accelerating decidualization by interacting with IGF1+ stromal cells, and observed that extravillous trophoblasts promote decidualization possibly by multiply pathways. Additionally, we developed a systematic repository of cell-cell communication for decidualization via the ligand-receptor complexes interactions. Our study provides deeper insights into the molecular and cellular characterizations during decidualization.

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Genome-wide Profiling of NR2F2 (COUP-TFII) Binding in Human Endometrial Stromal Cells [ChIP-Seq]

Project description:ChickenM-BM- ovalbumin upstream promoter-transcription factor II (COUP-TFII; NR2F2) is an orphan nuclear receptor involved in cell-fate specification, organogenesis, angiogenesis and metabolism. Ablation of COUP-TFII in the mouse uterus causes infertility due to defects in embryo attachment and impaired uterine stromal cell decidualization. Although the function of COUP-TFII in uterine decidualization has been described in mice, its role in the human uterus remains unknown. To better elucidate the mechanisms with which COUP-TFII regulates target gene transcription, genome-wide COUP-TFII binding sites in human endometrial stromal cells (HESC) treated with deciduogenic hormones were identified using ChIP-seq. A total of 16,298 intervals (binding regions) for COUP-TFII were identified compared with the input in HESC chromatin with a very low false discovery rate (0.17%) using a stringent cutoff of p =1x10-10. Distribution of intervals showed that more than half (58.6%) of the COUP-TFII binding sites are located within 10 kb of gene boundaries. 7.5% of total intervals reside within the 10 kb promoter region. A total of 6,077 unique genes were identified to have COUP-TFII binding sites within 10 kb of their gene boundaries. Examination of NR2F2 binding in pooled primary human endometrial stromal cells from 6 healthy women upon decidualization with a hormone cocktail of cAMP, E2 and medroxyprogesterone acetate.

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The differential expression of mRNAs and long noncoding RNAs between ectopic and eutopic endometrium of adenomyosis

Project description:Adenomyosis, defined as ectopic endometrial tissue within the myometrium, can often be misdiagnosed as multiple uterine leiomyomata or endometrial thickening. We therefore performed a combined mRNA and long noncoding (lnc)RNA microarray and bioinformatic analysis of eutopic and ectopic endometrium in women with adenomyosis to better understand its pathogenesis and help in the development of a semi-invasive diagnostic test. A total of 586 mRNAs were increased and 305 mRNAs decreased in ectopic endometrium of adenomyosis compared with eutopic endometrium, while 388 lncRNA transcripts were up-regulated and 188 down-regulated in ectopic compared with paired eutopic endometrial tissue. Bioinformatic analysis suggested a series of metabolic and molecular abnormalities in adenomyosis, which have many similarities with endometriosis. Furthermore, our study constitutes the first known report of lncRNA expression patterns in human adenomyosis ectopic and eutopic endometrial tissue. Two-condition experiment, ectopic endometrium vs. eutopic endometrium. 3 samples,self-control

2015-10-28 | E-GEOD-74373 | biostudies-arrayexpress

The role of Prokineticin 2 in endometrial decidualization

Project description:Recurrent implantation failure(RIF) is an urgent problem to be solved in reproduction.Currently, endometrium decidualization damage is considered as one of the important causes, but the mechanism is still unclear. Prokineticin 2(PK2) is a newly discovered secreted protein with multiple biological functions, and its role in the endometrium is unknown.Our previous study showed that PK2 was significantly increased in RIF patients, but endometrial decidualization markers PRL and IGFBP1 were lower compared with the control group. We performed transcriptome sequencing, we found there were significant differences between the PK2 overexpression group and the control group. Differential genes mainly involved in decidualization process including adhesion, immunity, chemotaxis, ect.

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Murine model of decidulization and menstruation

Project description:A murine model that mimic the decidualization and regression observed in human was used to investigate the molecular mechanisms underlying the dynamic processes in endometrium. Ovariectomized mice were treated sequentially with steroid hormones and then, to induce decidualization, oil was injected into the uterine lumen. A process similar to menstruation was induced by hormone-withdrawal. The uterine tissues were collected at 4 time-points after the induction of decidualization. Keywords: decidualization, menstruation, progesterone-withdrawal, time-course

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Tubal ectopic pregnancy as a model to identify endometrial genes and signaling pathways important in decidualization and regulated by local trophoblast

Project description:Gestation-matched endometrium was collected from women with ectopic pregnancy (EP) (n=11) and intrauterine pregnancies (IUP) (n=13). RNA was extracted from the tissue. In addition, tissues were prepared for histological analysis for degree of decidualization. We compared a) the samples from EP that were decidualized (n=6) with non-decidualized samples (n=5), and b) the decidualized EP (n=6) with decidualization-matched IUP (n=6) samples.

2011-07-01 | E-MTAB-680 | biostudies-arrayexpress

RNA sequencing of decidua reveals differentially expressed genes in recurrent pregnancy loss

Project description:Differentially expressed genes (DEGs) in decidua from recurrent pregnancy loss (RPL) patients by utilizing RNA sequencing (RNA-seq) technology have not been well characterized before.In the current study, four RPL patients and three control women were recruited to conduct RNA-seq, and 153 genes comprising 69 were upregulated and 84 downregulated showed different expression levels between the health control and RPL groups.

2022-11-01 | GSE161969 | GEO

Human primary endometrial stromal cells (proliferative vs secretory) LC-MSMS - proteins and phosphosites

Project description:Our study explores the phosphorylation pathways in decidualization, focussing on four major targets of interest – cAMP-dependent protein kinase, Rho-dependent protein kinase (ROCK), protein kinase B, and casein kinase 2. Our goal was to pinpoint the changes in protein kinase activity profile during decidualization in vitro and in vivo, and to establish how these changes are translated to the overall cellular phenotype and tissue morphology.

2021-06-21 | PXD026243 | Pride

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