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FOXO1 Regulates Uterine Epithelial Integrity and Progesterone Receptor Expression Critical for Embryo Implantation [RNA-seq]

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE72895 | 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 [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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Expression profiling of the uteri of progesterone induced uterine gland knockout mice

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

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

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Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation

Project description:Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation. In mice, the uterus becomes receptive to blastocyst implantation on day 4, but is refractory by day 5. Here, blastocysts could be recovered from progesterone-induced uterine gland (PUGKO) but not wildtype (WT) mice on day 5 post-mating. Anti-adhesive Muc1 protein and microvilli were present on the luminal epithelium of PUGKO but not WT uteri. A number of known uterine receptivity genes and gland-specific genes were altered in the PUGKO uterus. Next, the uterus and uterine luminal fluid (ULF) were obtained from WT and PUGKO mice on day 3, 4 and 5. Transcriptome analysis revealed that 580 genes were decreased in the PUGKO uterus, however ULF secrotome analysis revealed that many proteins and several amino acids were increased in the PUGKO ULF. Of note, many proteins encoded by many gland-specific genes were not identified in the ULF of WT mice. These results support the ideas that uterine glands secrete factors that regulate ULF homeostasis and interact with other cell types in the uterus to influence uterine receptivity and blastocyst implantation for the establishment of pregnancy.

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Constitutive expression of Progesterone Receptor B in the uterine epithelium prevents implantation by inhibiting estrogen regulation of LIF signaling [RNAseq-PRAoe_PRBoe_oil_P4]

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.

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