In vitro modelling of the human embryo implantation niche
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ABSTRACT:
PROVIDER: PRJEB71939 | ENA |
REPOSITORIES: ENA
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Project description:Single-cell RNA-sequencing (10X) data from a three-dimensional cell-engineered system for human implantation that closely recapitulates the cytoarchitecture and physiology of the receptive human endometrium
2024-07-17 | E-MTAB-13629 | biostudies-arrayexpress
Project description:Ineffective endometrial matrix remodeling, a key factor in infertility, impedes embryo implantation in the uterine wall. Our study reveals the cellular and molecular impact of human collagenase-1 administration in mouse uteri, demonstrating enhanced embryo implantation rates. Collagenase-1 promotes remodeling of the endometrial extracellular matrix (ECM), degrading collagen fibers and proteoglycans. This process releases matrix-bound bioactive factors, (e.g. VEGF, decorin), facilitating vascular permeability and angiogenesis. Collagenase-1 elevates embryo implantation regulators, including NK cell infiltration and the key cytokine LIF. Remarkably, uterine tissue maintains structural integrity despite reduced endometrial collagen fiber tension. In-utero collagenase-1 application rescues implantation in the heat stress and embryo transfer models, known for low implantation rates. Importantly, ex-vivo exposure of human uterine tissue to collagenase-1 induces collagen de-tensioning and VEGF release, mirroring remodeling observed in mice. Our research highlights collagenase potential to induce and orchestrate cellular and molecular processes enhancing uterine receptivity for effective embryo implantation. This innovative approach underscores ECM remodeling mechanisms critical for embryo implantation
2024-08-13 | PXD054389 | Pride
Project description:Endometrial receptivity plays a vital role in the success of embryo implantation. However, the temporal proteomic profile of porcine endometrium during embryo implantation is still unclear. In this study, the expression of proteins in endometrium on days 9, 10, 11, 12, 13, 14, 15 and 18 of pregnancy (D9, 10, 11, 12, 13, 14, 15 and 18) was profiled via iTRAQ technology. The results showed that 25, 55, 103, 91, 100, 120, 149 proteins were up-regulated, and 24, 70, 169, 159, 164, 161, 198 proteins were down-regulated in porcine endometrium on D10, 11, 12, 13, 14, 15 and 18 compared with that on D9, respectively. Among these differentially expressed (DE) proteins, MQM results indicated that S100A9, S100A12, HRG and IFI6 were differentially expressed in endometrial tissues during embryo implantation period. Bioinformatics analysis showed that the proteins differentially expressed in the 8 comparisons (D10 vs D9, D11 vs D9, D12 vs D9, D13 vs D9, D14 vs D9, D15 vs D9 and D18 vs D9) were involved in important processes and pathways related to immunization, endometrial remodeling, which have a vital effect on embryonic implantation. Our results reveal that RBP4 could regulate the cell proliferation, migration and apoptosis of endometrial epithelial cells and endometrial stromal cells to affect embryo implantation. This research also provides resources for studies of proteins in endometrium during early pregnancy.
2022-05-06 | PXD030681 | Pride
Project description:Direct analysis of the embryo-maternal interactions in a 3D biomimetic implantation niche
| PRJNA635496 | ENA
Project description:Extracellular vesicles (EVs) are important mediators of embryo attachment and outgrowth critical for successful implantation. While EVs have garnered immense interest in their therapeutic potential in assisted reproductive technology by improving implantation success, their large-scale generation remains a major challenge. Here, we report a rapid and scalable production of nanovesicles (NVs) from human trophectoderm cells (hTSCs) via membrane extrusion; these NVs can be generated in approximately 6 hours with a 20-fold higher yield than EVs isolated from the same number of cells. NVs display similar biophysical traits (morphologically intact, spherical, 90-130 nm) to EVs, and are laden with hallmark players of implantation (ITGA2/V, ITGB1, PRDX1, SOD2, and MFGE8) that include cell-matrix adhesion and extracellular matrix organisation proteins. Functionally, NVs are readily taken up by low-receptive endometrial HEC1A cells and reprogram their proteome towards a receptive phenotype that support hTSC spheroid attachment. Moreover, a single dose treatment of NVs significantly enhanced adhesion and spreading of mouse embryo trophoblast on fibronectin matrix. We show functional potential of NVs in enhancing embryo implantation and highlight their rapid and scalable generation, amenable to clinical utility.
2023-02-20 | PXD038856 | Pride
Project description:In vitro implantation model that recapitulates primary implantation events
| PRJNA1479856 | ENA
Project description:The early mammalian conceptus (blastocyst) contains two supporting extraembryonic tissues - the trophectoderm and the primitive endoderm (PrE) - that encase and guide the epiblast (Epi) to eventually form the all body. Modifications of the conceptus exposed key genes regulating these tissues co-development. However, the combination of signalling pathways at play remains elusive. Stem cell-based models including embryoid bodies and blastoids can be generated in large numbers and subjected to high-content screens. Here, we use combinatorial screens of proteins, GPCR ligands and small molecules to rapidly (<96 hours) and efficiently (80%) guide embryoid bodies to form a three dimensional PrE-/Epiblast-like niche in chemically-defined conditions (gel-free, serum-free). This bipotent niche spontaneously progresses, without growth factors, to form a pro-amniotic cavity surrounded by a polarized Epi covered by parietal and visceral endoderm-like cells. In blastoids, these molecules enhance the ratio and number of Gata6+/Nanog+ cells and promote the survival, expansion and morphogenesis of a post-implantation-like Epi in vitro. Altogether, modelling early development in chemically-defined conditions delineates the pathways sufficient to form a functional PrE/Epiblast niche that fuels post-implantation development.
2021-04-01 | GSE129655 | GEO
Project description:Our results indicated that a Nur77-derived phosphorylated peptide containing the phosphorylated T366 promotes epithelium-embryo adhesion both in vitro and in vivo, RNA-seq analysis was applied in the uterus samples from delayed implantation mouse model treated with pepetide-pThr366 or saline intrauterus injection.
2022-03-21 | GSE198602 | GEO
Project description:Mechanisms of implantation such as determination of the attachment pole, fetal-maternal communication, as well as underlying causes of implantation failure are largely unexplored. Here we performed single-cell RNA sequencing (scRNA-seq) on peri-implantation embryos from both humans and mice to explore trophectoderm development and embryo–endometrium crosstalk. We found that the transcriptomes of polar and mural trophectoderm (TE) diverged after embryos hatched from the zona pellucida in both species, with polar TE being more mature than mural TE. The implantation poles show similarities in cell cycle activities, as well as in expression of genes critical for implantation and placentation. Embryos that either fail to attach in vitro or fail to implant in vivo, show abnormalities in pathways related to energy production, protein metabolism and 18S rRNA m6A methylation. These findings uncover the gene expression characteristics of humans and mice TE differentiation during the peri-implantation period and provide new insights into embryo implantation.
2022-08-01 | GSE133200 | GEO
Project description:Embryo implantation in the rabbit is unique in that a typical fusion type of implantation is employed, in which trophoblast cells adhere and fuse to the apical surface of uterine epithelial cells. In the present study, we analyzed global gene expression changes in the rabbit uterus during embryo implantation by using RNA-seq.
2015-12-18 | GSE76115 | GEO