Bmp2 Is Critical for the Murine Decidual Response
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE10913 | GEO | 2008/03/21
SECONDARY ACCESSION(S): PRJNA107209
REPOSITORIES: GEO
Similar Datasets
Project description:The role of bone morphogenetic protein 2 (Bmp2)in regulating the transformation of the uterine stroma during embryo implantation in the mouse was investigated by the conditional ablation of Bmp2 in the uterus using the (PR-cre) mouse. Experiment Overall Design: Bmp2 gene ablation was confirmed by real-time PCR analysis in the PR-cre; Bmp2fl/fl (termed Bmp2d/d) uterus. While littermate controls average 0.9 litter of 6.2 ± 0.7 pups per month, Bmp2d/d females are completely infertile. Analysis of the infertility indicates that whereas embryo attachment is normal in the Bmp2d/d as in control mice, the uterine stroma is incapable of undergoing the decidual reaction to support further embryonic development. Recombinant human BMP2 can partially rescue the decidual response, suggesting that the observed phenotypes are not due to a developmental consequence of Bmp2 ablation. Microarray analysis demonstrates that ablation of Bmp2 leads to specific gene changes, including disruption of the Wnt signaling pathway, Progesterone receptor (PR) signaling, and the induction of prostaglandin synthase 2 (Ptgs2). Taken together, these data demonstrate that Bmp2 is a critical regulator of gene expression and function in the murine uterus.
2008-04-04 | E-GEOD-10913 | biostudies-arrayexpress
Project description:The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration. Gata2 gene ablation was confirmed by real-time PCR analysis in the PR-cre; Gata2fl/fl (termed Gata2d/d) uterus. While littermate controls are fertile, Gata2d/d females are completely infertile. Analysis of the infertility indicates that implantation does not occur, and the uterine stroma is incapable of undergoing the decidual reaction to support further embryonic development. Measure of P4 target genes including PR itself indicate a block in P4 target gene induction and that Gata2 regulates PR expression directly. Microarray analysis demonstrates that ablation of Gata2 leads to specific gene changes, including disruption of the Wnt signaling pathway, Progesterone receptor (PR) signaling, and Ihh signaling pathway. In addition we identified 46,183 GATA2 binding sites in P4 treatment conditions with 7,954 binding sites overlapping that of the PR.Taken together, these data demonstrate that Gata2 is a critical regulator of gene expression and function in the murine uterus.
2014-01-01 | E-GEOD-40659 | biostudies-arrayexpress
Project description:The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration. Gata2 gene ablation was confirmed by real-time PCR analysis in the PR-cre; Gata2fl/fl (termed Gata2d/d) uterus. While littermate controls are fertile, Gata2d/d females are completely infertile. Analysis of the infertility indicates that implantation does not occur, and the uterine stroma is incapable of undergoing the decidual reaction to support further embryonic development. Measure of P4 target genes including PR itself indicate a block in P4 target gene induction and that Gata2 regulates PR expression directly. Microarray analysis demonstrates that ablation of Gata2 leads to specific gene changes, including disruption of the Wnt signaling pathway, Progesterone receptor (PR) signaling, and Ihh signaling pathway. In addition we identified 46,183 GATA2 binding sites in P4 treatment conditions with 7,954 binding sites overlapping that of the PR.Taken together, these data demonstrate that Gata2 is a critical regulator of gene expression and function in the murine uterus.
2014-01-01 | E-GEOD-40660 | biostudies-arrayexpress
Project description:Implantation of an embryo in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands and receptors are expressed in the pregnant uterus, and BMP2 has been shown to be a key regulator of implantation. In this study, we investigated the roles of the BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy by producing uterine-specific Alk2 conditional knockout (cKO) mice. In the absence of ALK2, embryos can invade the uterine epithelium and stroma, but stromal cells cannot undergo uterine decidualization, resulting in sterility. Mechanistically, microarray analysis revealed that CCAAT/enhancer-binding protein β (Cebpb) expression is suppressed during decidualization in Alk2 cKO females. These findings and the similar phenotypes of Cebpb cKO and Alk2 cKO mice lead to the hypothesis that BMPs act upstream of C/EBPβ to regulate decidualization. To test this hypothesis, we knocked down ALK2 in human uterine stromal cells (HESC) and discovered that ablation of ALK2 alters HESC decidualization and suppresses CEBPB mRNA and protein levels. Chromatin immunoprecipitation (ChIP) analysis of decidualizing HESC confirmed that BMP signaling protein, SMAD1, directly regulates expression of CEBPB by binding a distinct regulatory sequence in the CEBPB promoter; C/EBPβ, in turn, regulates the expression of progesterone receptor (PGR). Our work clarifies the conserved mechanisms through which BMPs regulate embryo implantation in rodents and primates and, for the first time, uncovers a linear pathwayof BMP signaling through ALK2 to regulate CEBPB and, subsequently, PGR during decidualization. gene expression profiling of two groups: control mice and Alk2 cKO mice
2014-01-07 | E-GEOD-46689 | biostudies-arrayexpress
Project description:Implantation of an embryo in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands and receptors are expressed in the pregnant uterus, and BMP2 has been shown to be a key regulator of implantation. In this study, we investigated the roles of the BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy by producing uterine-specific Alk2 conditional knockout (cKO) mice. In the absence of ALK2, embryos can invade the uterine epithelium and stroma, but stromal cells cannot undergo uterine decidualization, resulting in sterility. Mechanistically, microarray analysis revealed that CCAAT/enhancer-binding protein β (Cebpb) expression is suppressed during decidualization in Alk2 cKO females. These findings and the similar phenotypes of Cebpb cKO and Alk2 cKO mice lead to the hypothesis that BMPs act upstream of C/EBPβ to regulate decidualization. To test this hypothesis, we knocked down ALK2 in human uterine stromal cells (HESC) and discovered that ablation of ALK2 alters HESC decidualization and suppresses CEBPB mRNA and protein levels. Chromatin immunoprecipitation (ChIP) analysis of decidualizing HESC confirmed that BMP signaling protein, SMAD1, directly regulates expression of CEBPB by binding a distinct regulatory sequence in the CEBPB promoter; C/EBPβ, in turn, regulates the expression of progesterone receptor (PGR). Our work clarifies the conserved mechanisms through which BMPs regulate embryo implantation in rodents and primates and, for the first time, uncovers a linear pathwayof BMP signaling through ALK2 to regulate CEBPB and, subsequently, PGR during decidualization.
2014-01-07 | GSE46689 | GEO
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.
2020-07-08 | GSE146650 | GEO
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
Project description:Our preliminary study revealed that the homeobox transcription factors, Msx1 and Msx2, are expressed in the mouse uterus during early pregnancy. Further, conditional deletion of Msx1 and Msx2 in mouse uterus leads to implantation failure due to impaired uterine epithelial receptivity. To identify the downstream targets of Msx1Msx2 in the uterus, we performed gene expression profling of uterine stromal cells isolated from Msx1Msx2-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 and Wnts in uterine stroma of Msx1Msx2-ablated mice. We performed conditional ablation of Msx1Msx2 in the mouse uterus using the PRcre mouse model. 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.
2014-07-20 | E-GEOD-30966 | biostudies-arrayexpress
Project description:The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration.
2014-01-01 | GSE40660 | GEO
Project description:The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration.
2014-01-01 | GSE40659 | GEO