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FOXO1 Regulates Attachment of the Implanting Blastocyst to the Endometrium at the Window of Receptivity

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

ORGANISM(S): Mus musculus

PROVIDER: GSE72896 | GEO | 2018/10/15

REPOSITORIES: GEO

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FOXO1 Regulates Attachment of the Implanting Blastocyst to the Endometrium at the Window of Receptivity

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-07-03 | E-GEOD-72896 | biostudies-arrayexpress

FOXO1 Regulates Attachment of the Implanting Blastocyst to the Endometrium at the Window of Receptivity [RNA-seq]

Project description:We report the sequencing of the uterine transcriptome sequencing of control and conditional knock-out of the Forkhead box O1 at day 4.5 of murine pseudopregnancy RNA was isolated from day 4.5 Pseudopregnancy adult females. RNA from two females was pooled per sample. Three samples per genotype were sequenced for differential gene expression analysis.

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FOXO1 Regulates Attachment of the Implanting Blastocyst to the Endometrium at the Window of Receptivity [ChIP-seq]

Project description:We report the whole genome binding profile of the Forkhead Box O1 ChIP-seq in murine endometrium

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Decreased epithelial progesterone receptor A at the window of receptivity is required for preparation of the endometrium for embryo attachment.

Project description:The precise timing of progesterone signaling through its cognate receptor, the progesterone receptor (PGR), is critical for the establishment and maintenance of pregnancy. Loss of PGR expression in the murine uterine epithelium during the preimplantation period is a marker for uterine receptivity and embryo attachment. We hypothesized that the decrease in progesterone receptor A (PGRA) expression is necessary for successful embryo implantation. To test this hypothesis, a mouse model constitutively expressing PGRA (mPgrALsL/+) was generated. Expression of PGRA in all uterine compartments (Pgrcre) or uterine epithelium (Wnt7acre) resulted in infertility with defects in embryo attachment and stromal decidualization. Expression of critical PGRA target genes, indian hedgehog, and amphiregulin (Areg), was maintained through the window of receptivity while the estrogen receptor target gene, the leukemia inhibitory factor (Lif), a key regulator of embryo receptivity, was decreased. Transcriptomic and cistromic analyses of the mouse uterus at day 4.5 of pregnancy identified an altered group of genes regulating molecular transport in the control of fluid and ion levels within the uterine interstitial space. Additionally, LIF and its cognate receptor, the leukemia inhibitory factor receptor (LIFR), exhibited PGR-binding events in regions upstream of the transcriptional start sites, suggesting PGRA is inhibiting transcription at these loci. Therefore, downregulation of the PGRA isoform at the window of receptivity is necessary for the attenuation of hedgehog signaling, transcriptional activation of LIF signaling, and modulation of solutes and fluid, producing a receptive environment for the attaching embryo.

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Decreased epithelial Progesterone Receptor A at the window of receptivity is required for preparation of the endometrium for embryo attachment

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.

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Decreased MUC1 in endometrium is an independent receptivity marker in recurrent implantation failure during implantation window.

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