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The role of epithelial Progesterone Receptor Isoforms in embryo implantation [ChIPseq-PGR-H3K27AC]

ABSTRACT: The role of epithelial Progesterone Receptor Isoforms in embryo implantation [ChIPseq-PGR-H3K27AC]

PROVIDER: PRJNA739579 | ENA |

REPOSITORIES: ENA

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Genome-wide binding sites of Progesterone receptor (PGR) isoforms PGR-A and PGR-B during differentiation of human endometrial stromal cells

Project description:We report the genome-wide binding sites of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells that express either PGR-A or PGR-B. Progesterone, acting through the progesterone receptors (PGRs), is one of the most critical regulators of endometrial differentiation, known as decidualization, which is a key step toward the establishment of pregnancy. Yet a long-standing unresolved issue in uterine biology is the precise roles played by the major PGR isoforms, PGR-A and PGR-B, during decidualization in the human. Our approach, expressing PGR-A and PGR-B individually after silencing endogenous PGRs in human endometrial stromal cells (HESC), enabled the analysis of the roles of these isoforms separately as well as jointly by ChIP-seq and gene-expression analysis. In order to study the cistromes of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells, we generated primary cultures of human endometrial stromal cells expressing flag tagged PGR-A and PGR-B individually after silencing endogenous PGRs. Input DNA was used as the reference sample.

2015-04-27 | E-GEOD-62475 | biostudies-arrayexpress

Genome-wide binding sites of Progesterone receptor (PGR) isoforms PGR-A and PGR-B during differentiation of human endometrial stromal cells

2015-04-27 | GSE62475 | GEO

The role of epithelial Progesterone Receptor Isoforms in embryo implantation [ChIPseq-PGR-H3K27AC]

Project description:RNA-seq analysis of uterine luminal epithelium at D4.5 indicates that epithelial PGRA and PGRB shares conseved pathways. Constitutive epithelial PGRA and PGRB disrupts the embryo implantation both through the suppressed FOXO1 signaling by excluding FOXO1 from the nuclear at the uterine epithelium. There are three layers of regulation. Firstly, PGRA and PGRB diminishes Lif transcription in uterine glands by blocking ESR1 binding at the Lif promoter at D3.5 which is critical for the FOXO1 nuclear expression at D4.5 through LIF/pSTAT3/FOXO1. Secondly, PGRA and PGRB directly suppres Foxo1 transcription at the uterine epithelium probably through direct binding at Foxo1 promoter. Thirdly, PGRA and PGRB promotes the Sgk1 transcription, the kinases that phosphorylate FOXO1 to translocate it into cytoplasma for degradation.

2021-12-02 | GSE178538 | GEO

TRIM28 modulates progesterone and estrogen signaling in endometrium [mouseD35-PGR-ChIPseq-mm10]

Project description:TRIM28 interacts with PGR and ESR1 in both human and mouse uterus to modulate estrogen and progesterone signaling. Knocking down of TRIM28 in the human endometrial stromal cells impaired decidualization in vitro. Deletion of TRIM28 from mouse uterus disrupted uterine stromal decidualization leading to infertility. Additionally, TRIM28 deletion caused abnormal accumulation of TRIM28 positive and PGR negative cells in the stroma.

2023-06-04 | GSE226623 | GEO

The role of epithelial Progesterone Receptor Isoforms in embryo implantation

Project description:The role of epithelial Progesterone Receptor Isoforms in embryo implantation

| PRJNA739574 | ENA

Gene expression analysis of granulosa cells from animals that are wildtype or knockout for total PGR, PGR-A or PGR-B (RNA-seq)

Project description:Progesterone receptor (PGR) is essential for various functions in the female reproductive tract, especially ovulation in the ovary. PGR consists of two main isoforms, PGR-A and PGR-B, that possess different expression patterns and are responsible for various unique roles in different tissue contexts. While both are present in the reproductive tract, PGR-A is the only one known to be essential for ovulation while PGR-B plays a lesser role in the reproductive tract. However, the specific roles of PGR isoforms on gene expression in peri-ovulatory granulosa cells have not been previously investigated in detail. In this study, we identified the unique role of PGR-A and PGR-B in peri-ovulatory granulosa cells through RNA-seq of knockout mouse models for total PGR (PGR KO) or specific isoforms (PGR-A KO and PGR-B KO)

2022-05-18 | GSE168213 | GEO

The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-Foxo1dd_LE]

Project description:The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-Foxo1dd_LE]

| PRJNA739582 | ENA

The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-ePRAoe_ePRBoe_LE]

Project description:The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-ePRAoe_ePRBoe_LE]

| PRJNA739580 | ENA

Myometrial Progesterone Receptor Isoform B Regulates the Phospholipase C Pathway and Suppresses Uterine Contractility

Project description:Uterine contractile dysfunction leads to pregnancy complications such as preterm birth and labor dystocia. Progesterone is necessary to suppress uterine contractions to prevent premature labor. As humans maintain high levels of progesterone throughout parturition, a functional progesterone withdrawal hypothesis suggests that relative levels of myometrial progesterone receptor isoforms PGR-A and PGR-B switch at parturition, where PGR-B promotes a relaxed state and PGR-A result in increased uterine contractility. Our objective is to determine the effects of altered levels of PGR-B and PGR-A in the mouse myometrium on pregnancy and parturition using transgenic mouse models in which the relative levels of these isoforms are altered specifically in the myometrium. Overexpression of PGR-B is associated with a markedly increased gestational length compared to control mice. In both ex vivo and in vivo experiments, myometrium of PGR-B overexpressing mice have prolonged labor, a significant decrease in uterine contractility, and a high incidence of labor dystocia. Conversely, overexpression of PGR-A is associated with an increase in uterine contractility without a change in gestational length. Uterine RNAseq at mid-pregnancy identified isoform-specific downstream targets and genes that were commonly regulated by both PGR isoforms. Gene signature analyses further revealed that PGR-B promotes muscle relaxation and that PGR-A is pro-inflammation. High levels of PGR-B manifest a genetic profile of a blunted phospholipase C pathway that mediates oxytocin and angiotensin II induced muscle contraction. These findings provided in vivo support that PGR isoform levels determine distinct transcriptomic landscapes and pathways in myometrial function and labor.

2021-02-24 | GSE146634 | GEO

TRIM28 modulates progesterone and estrogne signaling in endometrium [mouseD35-ChIPseq-mm10]

Project description:TRIM28 interacts with PGR and ESR1 in both human and mouse uterus to modulate estrogen and progesterone signaling. Knocking down of TRIM28 in the human endometrial stromal cells imparied decidualization in vitro. Deletion of TRIM28 from mouse uterus disrupted uterine stromal decidualization leading to infertility. Addtionally, TRIM28 deletion caused abnormal accumulation of TRIM28 postive and PGR negative cells in the stroma.

2023-06-04 | GSE205476 | GEO

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