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The role of epithelial Progesterone Receptor Isoforms in embryo implantation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE178542 | GEO | 2021/12/02

REPOSITORIES: GEO

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The role of epithelial progesterone receptor isoforms in embryo implantation.

Project description:The loss of uterine epithelial progesterone receptor (PGR) is crucial for successful embryo implantation in both humans and mice. The two major isoforms PGRA and PGRB have divergent functions under both physiological and pathological conditions. The present study compares phenotypes and gene signatures of PGRA and PGRB in uterine epithelium using uterine epithelial-specific constitutively expressed PGRA or PGRB mouse models. The cistrome and transcriptome analysis reveals substantial overlap between epithelial PGRA and PGRB, and both disrupt embryo implantation through FOXO1 pathways. Constitutive epithelial PGRA and PGRB expression impairs ESR1 occupancy at the promoter of Lif leading to reduced Lif transcription and further exaggerates SGK1 expression leading to enhanced PI3K-SGK1 activities, and both contribute to the decline of nuclear FOXO1 expression. Our study demonstrates that PGRA and PGRB in the uterine epithelium act on a similar set of target genes and commonly regulate the LIF-SGK1-FOXO1 signaling pathway for embryo implantation.

| S-EPMC8661479 | biostudies-literature

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

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 | GSE178540 | GEO

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

2021-12-02 | GSE178539 | GEO

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

2021-12-02 | GSE178538 | 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

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

FOXO1 regulates uterine epithelial integrity and progesterone receptor expression critical for embryo implantation.

Project description:Successful embryo implantation requires a receptive endometrium. Poor uterine receptivity can account for implantation failure in women who experience recurrent pregnancy loss or multiple rounds of unsuccessful in vitro fertilization cycles. Here, we demonstrate that the transcription factor Forkhead Box O1 (FOXO1) is a critical regulator of endometrial receptivity in vivo. Uterine ablation of Foxo1 using the progesterone receptor Cre (PgrCre) mouse model resulted in infertility due to altered epithelial cell polarity and apoptosis, preventing the embryo from penetrating the luminal epithelium. Analysis of the uterine transcriptome after Foxo1 ablation identified alterations in gene expression for transcripts involved in the activation of cell invasion, molecular transport, apoptosis, ?-catenin (CTNNB1) signaling pathway, and an increase in PGR signaling. The increase of PGR signaling was due to PGR expression being retained in the uterine epithelium during the window of receptivity. Constitutive expression of epithelial PGR during this receptive period inhibited expression of FOXO1 in the nucleus of the uterine epithelium. The reciprocal expression of PGR and FOXO1 was conserved in human endometrial samples during the proliferative and secretory phase. This demonstrates that expression of FOXO1 and the loss of PGR during the window of receptivity are interrelated and critical for embryo implantation.

| S-EPMC6277115 | biostudies-literature

Progesterone Receptor Isoforms, Agonists and Antagonists Differentially Reprogram Estrogen Signaling.

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-12-31 | GSE80620 | GEO

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

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

| PRJNA739579 | ENA