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Project description:Early gestational loss occurs in approximately 20% of all clinically recognized human pregnancies and is an important cause of morbidity. Either embryonic or maternal defects can cause loss, but a functioning and receptive uterine endometrium is crucial for embryo implantation. We report that the switch/sucrose nonfermentable (SWI/SNF) remodeling complex containing polybromo-1 (PBRM1) and Brahma-related gene 1 (BRG1) is essential for implantation of the embryonic blastocyst on the wall of the uterus in mice. Although preimplantation development is unaffected, conditional ablation of Pbrm1 in uterine stromal cells disrupts progesterone pathways and uterine receptivity. Heart and neural crest derivatives expressed 2 (Hand2) encodes a basic helix-loop-helix (bHLH) transcription factor required for embryo implantation. We identify an enhancer of the Hand2 gene in stromal cells that requires PBRM1 for epigenetic histone modifications/coactivator recruitment and looping with the promoter. In Pbrm1cKO mice, perturbation of chromatin assembly at the promoter and enhancer sites compromises Hand2 transcription, adversely affects fibroblast growth factor signaling pathways, prevents normal stromal-epithelial crosstalk, and disrupts embryo implantation. The mutant female mice are infertile and provide insight into potential causes of early pregnancy loss in humans.
| S-EPMC10904057 | biostudies-literature
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.
2024-01-14 | GSE229369 | GEO
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.
2024-01-14 | GSE229368 | GEO
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.
2024-01-14 | GSE229367 | GEO
Project description:Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in mouse uterus
| PRJNA954279 | ENA
Project description:Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in mouse uterus [CHIC-Seq]
| PRJNA954289 | ENA
Project description:Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in mouse uterus [ATAC-Seq]
| PRJNA954283 | ENA
Project description:Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in mouse uterus [RNA-Seq]
| PRJNA954288 | ENA
Project description:ATF6?, one of the sensor proteins in the stress signaling pathway of the endoplasmic reticulum, is located in the membrane of the endoplasmic reticulum. To date, the physiological function of ATF6? in the process of embryo implantation has not been reported.In this study, the expression pattern of ATF6? in the mouse uterus during peri-implantation and the estrous cycle was detected by real-time PCR, western blot and immunohistochemistry.ATF6? mRNA and protein levels were higher in the uterus near the implantation site on day 5 and were intensely expressed in the secondary decidual zone (SDZ) on days 7-8. In the uteri of pseudopregnant mice, ATF6? mRNA and protein levels were lower on day 5 than on other days. The activating blastocyst and artificial decidualization had an obvious effect of increasing the expression of ATF6?. In addition, the expression of ATF6? was affected by progesterone (P4) and estrogen (E2) in ovariectomized mice. This finding is further supported by evidence from mice during the estrous cycle.Thus, we have concluded that ATF6? may play an important role during embryo implantation and decidualization.
| S-EPMC5055674 | biostudies-literature
Project description:BackgroundEmbryo implantation into the uterus is a crucial step for human reproduction. A hypothesis has been proposed that the molecular circuit invented by trophoblasts for invasive embryo implantation during evolution might be misused by cancer cells to promote malignancy. Unfortunately, our current understanding of the molecular mechanism underlying embryo implantation is far from complete.ResultsHere we used the mouse as an animal model and generated a single-cell transcriptomic atlas of the embryo implantation site of mouse uterus at the invasion phase of embryo implantation on gestational day 6. We revealed 23 distinct cell clusters, including 5 stromal cell clusters, 2 epithelial cell clusters, 1 smooth muscle cell cluster, 2 pericyte clusters, 4 endothelial cell clusters, and 9 immune cell clusters. Through data analysis, we identified differentially expression changes in all uterine cell types upon embryo implantation. By integrated with single-cell RNA-seq data from E5.5 embryos, we predicted cell-cell crosstalk between trophoblasts and uterine cell types.ConclusionsOur study provides a valuable resource for understanding of the molecular mechanism of embryo implantation.
| S-EPMC8817544 | biostudies-literature