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Gene expression profiling of uterine stromal cells isolated from Hand2 floxed and Hand2 ablated mice on day 4 of pregnancy

ABSTRACT: Our previous study revealed that the basic helix-loop-helix transcription factor Hand2 is a downstream target of progesterone signaling in mouse uterine stroma at the time of implantation. Further, conditional deletion of Hand2 in mouse uterus leads to implantation failure due to impaired uterine epithelial receptivity. To identify the downstream targets of Hand2 in the uterus, we performed gene expression profling of uterine stromal cells isolated from Hand2-null mice and the corresponding controls on day4 of pregnancy (the time of implantation). The microarray results revealed elevated expression of mRNAs corresponding to several members of the fibroblast growth factor family in uterine stroma of Hand2-ablated mice. These factors act as paracrine mediators of mitogenic effects of estrogen on the epithleium. Thus, Hand2 is a critical regulator of the uteirne stromal-epithelial communication that directs proper steroid regulation conducive for establshment of pregnancy.

ORGANISM(S): Mus musculus

PROVIDER: GSE25881 | GEO | 2011/06/03

SECONDARY ACCESSION(S): PRJNA135811

REPOSITORIES: GEO

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Gene expression profiling of uterine stromal cells isolated from Hand2 floxed and Hand2 ablated mice on day 4 of pregnancy

Project description:Our previous study revealed that the basic helix-loop-helix transcription factor Hand2 is a downstream target of progesterone signaling in mouse uterine stroma at the time of implantation. Further, conditional deletion of Hand2 in mouse uterus leads to implantation failure due to impaired uterine epithelial receptivity. To identify the downstream targets of Hand2 in the uterus, we performed gene expression profling of uterine stromal cells isolated from Hand2-null mice and the corresponding controls on day4 of pregnancy (the time of implantation). The microarray results revealed elevated expression of mRNAs corresponding to several members of the fibroblast growth factor family in uterine stroma of Hand2-ablated mice. These factors act as paracrine mediators of mitogenic effects of estrogen on the epithleium. Thus, Hand2 is a critical regulator of the uteirne stromal-epithelial communication that directs proper steroid regulation conducive for establshment of pregnancy. We performed conditional ablation of Hand2 in the mouse uterus using the PRcre mouse model. As Hand2 expression is restricted to stromal comaprtment, we isolated uterine stromal cells from day4 pregnant mice (n=5 for each genotype), purified total RNA from these cells, pooled these samples and then hybridized to high density affymetrix microarrays. Control vs. KO.

2011-06-03 | E-GEOD-25881 | biostudies-arrayexpress

Gene expression profiling of uterine stromal cells isolated from Msx1Msx2 floxed and Msx1Msx2 ablated mice on day 4 of pregnancy

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2014-07-20 | E-GEOD-30966 | biostudies-arrayexpress

Gene expression profiling of uterine stromal cells isolated from Msx1Msx2 floxed and Msx1Msx2 ablated mice on day 4 of pregnancy

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Gene expression profiling of mouse uterine stromal cells isolated on day 5 of pregnancy

Project description:Our study revealed that hypoxia inducible factor 2 alpha, Hif2 alpha, is a downstream target of estrogen signaling in mouse uterine stroma at the time of implantation. Further, conditional deletion of Hif2 alpha in mouse uterus leads to infertility due to impaired epithelial remodeling at the time of implantation. To identify the downstream targets of Hif2 alpha in the uterus, we performed gene expression profiling of uterine stromal cells isolated from Hif2 alpha-intact and -null mice on day 5 of pregnancy, overlapping the window of implantation. The microarray results revealed altered expression of mRNAs corresponding to factors involved in protein trafficking in uterine stroma of Hif2 alpha-ablated mice. These factors mediate crosstalk between uterine storma and epithelial cells to promote epithelial remodeling and implantation. Thus, Hif2 alpha regulates embryo implantation by controlled trafficking of secretory granules during early pregnancy.

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Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in mouse uterus [CHIC-Seq]

Project description:Early gestational loss occurs in ~20% of all clinically recognized human pregnancies and is a significant cause of morbidity. Either embryonic or maternal defects can cause loss, but a functioning and receptive uterine endometrium is crucial for embryo implantation. The SWI/SNF remodeling complex containing PBRM1and BRG1 is essential for implantation of the embryonic blastocyst on the wall of the uterus in mice. Although pre-implantation development is unaffected, conditional ablation of Pbrm1 in uterine stromal cells disrupts progesterone pathway and uterine receptivity. Hand2 is a bHLH transcription factor required for embryo implantation. We report a new enhancer of Hand2 in stromal cells that requires PBRM1 for epigenetic histone modifications and coactivator recruitment. In Pbrm1cKO mice, perturbations at the enhancer site compromised Hand2 transcription, disrupts the fibroblast growth factor signaling pathway and prevents normal Stromal- Epithelial crosstalk and embryo implantation. The resultant mutant female mice are infertile and provide insight into potential causes of early pregnancy loss in humans.

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Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in mouse uterus [ATAC-Seq]

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Gene expression profiling of uterine epithelial cells isolated from Msx1Msx2 floxed and Msx1Msx2 ablated mice on day 4 of pregnancy

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