The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-Foxo1dd_LE]
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ABSTRACT:
PROVIDER: PRJNA739582 | ENA |
REPOSITORIES: ENA
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Project description:The role of epithelial Progesterone Receptor Isoforms in embryo implantation
| PRJNA739574 | ENA
Project description:The role of epithelial Progesterone Receptor Isoforms in embryo implantation [RNAseq-ePRAoe_ePRBoe_LE]
| PRJNA739580 | ENA
Project description:The role of epithelial Progesterone Receptor Isoforms in embryo implantation [ChIPseq-PGR-H3K27AC]
| PRJNA739579 | ENA
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
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 | GSE178539 | GEO
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
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
Project description:Ineffective endometrial matrix remodeling, a key factor in infertility, impedes embryo implantation in the uterine wall. Our study reveals the cellular and molecular impact of human collagenase-1 administration in mouse uteri, demonstrating enhanced embryo implantation rates. Collagenase-1 promotes remodeling of the endometrial extracellular matrix (ECM), degrading collagen fibers and proteoglycans. This process releases matrix-bound bioactive factors, (e.g. VEGF, decorin), facilitating vascular permeability and angiogenesis. Collagenase-1 elevates embryo implantation regulators, including NK cell infiltration and the key cytokine LIF. Remarkably, uterine tissue maintains structural integrity despite reduced endometrial collagen fiber tension. In-utero collagenase-1 application rescues implantation in the heat stress and embryo transfer models, known for low implantation rates. Importantly, ex-vivo exposure of human uterine tissue to collagenase-1 induces collagen de-tensioning and VEGF release, mirroring remodeling observed in mice. Our research highlights collagenase potential to induce and orchestrate cellular and molecular processes enhancing uterine receptivity for effective embryo implantation. This innovative approach underscores ECM remodeling mechanisms critical for embryo implantation
2024-08-13 | PXD054389 | Pride
Project description:Endometrial receptivity plays a vital role in the success of embryo implantation. However, the temporal proteomic profile of porcine endometrium during embryo implantation is still unclear. In this study, the expression of proteins in endometrium on days 9, 10, 11, 12, 13, 14, 15 and 18 of pregnancy (D9, 10, 11, 12, 13, 14, 15 and 18) was profiled via iTRAQ technology. The results showed that 25, 55, 103, 91, 100, 120, 149 proteins were up-regulated, and 24, 70, 169, 159, 164, 161, 198 proteins were down-regulated in porcine endometrium on D10, 11, 12, 13, 14, 15 and 18 compared with that on D9, respectively. Among these differentially expressed (DE) proteins, MQM results indicated that S100A9, S100A12, HRG and IFI6 were differentially expressed in endometrial tissues during embryo implantation period. Bioinformatics analysis showed that the proteins differentially expressed in the 8 comparisons (D10 vs D9, D11 vs D9, D12 vs D9, D13 vs D9, D14 vs D9, D15 vs D9 and D18 vs D9) were involved in important processes and pathways related to immunization, endometrial remodeling, which have a vital effect on embryonic implantation. Our results reveal that RBP4 could regulate the cell proliferation, migration and apoptosis of endometrial epithelial cells and endometrial stromal cells to affect embryo implantation. This research also provides resources for studies of proteins in endometrium during early pregnancy.
2022-05-06 | PXD030681 | Pride
Project description:The progesterone receptor A (PGRA) isoform is the dominantly expressed isoform within the mouse uterus and is indispensable for uterine function and fertility in the murine reproductive tract. During early pregnancy, the PGRA isoform is spatiotemporally expressed in the uterine epithelium. At days 2-3 of pregnancy, PGRA is upregulated within the epithelium and then decreases before day 4, the day of embryo implantation. This decrease of PGRA has been recognized as a marker to initiate the time in which the uterus is receptive to the embryo, yet this has never been functionally tested. We hypothesized the decrease of PGRA at the window of receptivity is required for successful embryo implantation. In order to test this hypothesis, we generated a PGRA conditional expression allele initiated by Cre recombinase present in the uterine epithelial compartment. The PGRA expressing mice exhibited infertility with the inability to undergo embryo implantation or decidualization. RNA microarray and ChIP-Seq analyses were utilized to identify the differentially regulated pathways controlled by PGRA at the time of implantation.
2019-08-29 | GSE86303 | GEO