Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HB-EGF-loaded nanovesicles enhance trophectodermal spheroid attachment and invasion

ABSTRACT: The ability of trophectodermal cells (outer layer of the embryo) to attach to the endometrial cells and subsequently invade the underlying matrix are critical stages of embryo implantation during successful pregnancy establishment. Extracellular vesicles (EVs) have been implicated in embryo-maternal crosstalk, that reprogram endometrial cells towards a pro-implantation signature and phenotype. However, challenges associated with EV yield and direct loading of biomolecules limits their therapeutic potential. We have previously established generation of cell-derived nanovesicles (NVs) from human trophectodermal cells (hTSCs) and their capacity to reprogram endometrial cells to enhance adhesion and blastocyst outgrowth. Here, we developed a rapid NV loading strategy to encapsulate potent implantation molecules such as HB-EGF (NVHBEGF). We show these loaded NVs upon uptake to low-receptive endometrial HEC1A cells elicit EGFR-downstream pathways and enhance target cell attachment and invasion in an EGF-signalling dependent manner. This phosphoproteomics and proteomics approach reveals that NVHBEGF regulate short-term signalling (e.g., ERBB/EGFR signalling) and long-term reprogramming capabilities on endometrial cells, and demonstrate their functional regulation on trophectodermal-endometrial interactions and trophectodermal invasion. This proof-of-concept study demonstrate feasibility in enhancing the potency of NVs in the context of embryo attachment and establishment.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: David Greening

PROVIDER: MSV000092562 | MassIVE | Mon Jul 31 18:23:00 BST 2023

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Similar Datasets

SECRETORY PROTEOMIC RESPONSES OF ENDOMETRIAL EPITHELIAL CELLS TO TROPHOBLAST DERIVED EXTRACELLULAR VESICLES

Project description:Synchronized cross talk between embryo and endometrium during pre-implantation period is critical for establishment of pregnancy. Extracellular vesicels(EVs) of both embryo and endometrial origin are known to be integral in regulating embryo maternal communication during this time. However, exact molecular signalling pathways or factors that regulate the embryo endometrial communication during pre-conception period remains elusive. Here in this study extracellular vesicles from trophoblast cells were shown to modulate endometrial epithelial cell secretome in favour of embryo implantation and embryo development.

2023-10-24 | PXD040311 | Pride

Functional nanovesicles from human trophectodermal cells for embryo implantation

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

Human trophectoderm extracellular vesicle proteome

Project description:Embryo implantation into maternal endometrium is critical for initiation and establishment of pregnancy, requiring developmental synchrony between endometrium and blastocyst. However, factors regulating human endometrial-embryo cross talk and facilitate implantation remain largely unknown. Extracellular vesicles (EVs) are emerging as important mediators of this process. Here, human trophectomderm stem cell-derived EVs were shown to transfer to and regulate human endometrial cells towards processes associated with implantation. Importantly, transfer of trophectoderm EV cargo proteins to endometrial cells to mediate changes in polarity is demonstrated.

2021-03-18 | PXD022501 | Pride

The analysis of the α2,6-sialylated proteins in endometrium from porcine gestational day 15 by LC-MS/MS

Project description:Implantation is the attachment of embryo in the endometrium. Failure in implantation is a major cause of early pregnancy loss. During implantation, the temporal uterine lumen closure can help embryo attach to the uterus. In pigs, extending of endometrial folds to form interlocking finger-like projections is a main cause leads to uterine lumen closure during attachment time, but the underlying mechanisms are largely unknown. Our data reveal that pig uterine luminal epithelium (LE) migrate in coordinated groups during extending of endometrial folds. Moreover, the MALDI-TOF MS based N-glycomic characterization of porcine endometrium revealed α2,6-linked sialic acid are highly expressed in pig uterine LE during extending of endometrial folds. To investigated the mechanisms by which α2,6-sialylated proteins in formation of the endometrial folding during implantation in pigs, the α2,6-sialylated proteins in pig uterine LE were characterized by proteomic analysis and those proteins that are involved in cell adhesion, such as E-cadherin, were detected. Finally, our in vivo and in vitro data show that α2,6-sialylation of E-cadherin occurs in accompany with collective epithelial migration. The results provide new insight into the mechanism of pig implantation by identifying that α2,6-sialylation of cell adhesion molecules may participate in formation of extending of endometrial folds through promoting of collective migration of uterine LE.

2022-02-17 | PXD027571 | Pride

human embryo proteome reprogramming by endometrial extracellular vesicles

Project description:- Endometrial sEV protein cargo are hormonally regulated – EP treated sEVs are enriched in key players of embryo implantation - Endometrial sEVs are taken up by recipient trophectoderm cells - Endometrial EP-sEVs (or secretory phase sEVs) promote trophectoderm cell invasion via MAPK signalling pathway - Invasion-related proteins are enriched on Tsc cell surface following EP-sEV treatment

2021-11-17 | PXD027642 | Pride

Gene expression analysis of an endometrial cell line

Project description:This group is studying the role of glycoproteins in embryo implantation and development of the maternal-fetal interface. The Aplin lab is developing an embryo implantation model in which blastocysts attach to human endometrial cells. The project aims to investigate the molecular interactions mediating attachment and subsequent events including trophoblast invasion and displacement of maternal cells. In the present phase of the project, the lab is using the Ishikawa (human endometrial) cell line with mouse embryos.

2011-04-29 | GSE28925 | GEO

Gene expression analysis of an endometrial cell line

2011-04-29 | E-GEOD-28925 | biostudies-arrayexpress

Podocalyxin governs the barrier function of human endometrial epithelium and critically regulates receptivity for embryo implantation

Project description:Embryo implantation is a key step in establishing pregnancy and a major limiting factor in IVF. Implantation requires the endometrium, the inner lining of the uterus, to transform from a non-receptive to a receptive state, to allow embryos to attach to the surface and enter into the tissue. However, the fundamental mechanisms governing receptivity are not well understood. Here we show that transmembrane protein podocalyxin is a major and clinically significant factor regulating human endometrial receptivity. Podocalyxin is expressed in all endometrial epithelial cells in the non-receptive state but is selectively down-regulated in the luminal epithelium at receptivity. We present evidence that podocalyxin critically governs the barrier function of the endometrial epithelium, likely as an intrinsic protective mechanism, rendering it non-receptive to an embryo. In addition, podocalyxin suppresses genes promoting receptivity (eg LIF, CSF1) but stimulates those inhibiting implantation (eg WNT7A, LEFTY2). Down-regulation of podocalyxin in the luminal epithelium, likely mediated by progesterone, selectively converts the endometrial surface to a more adhesive state that facilitates embryo attachment and penetration. Furthermore, inadequate down-regulation of podocalyxin in the endometrial luminal epithelium is associated with poorer implantation rates in IVF. We thus propose that podocalyxin promotes the barrier function of human endometrial epithelial cells and critically regulates receptivity for embryo implantation.

2021-04-01 | GSE148274 | GEO

Endometrial extracellular vesicle decidualization

Project description:Proper decidualization is vital in preparation for a potential embryo receptivity, placentation, menstrual health and subsequent endometrial regeneration. Given the importance of extracellular vesicles (EVs) in intercellular communication, and recently in embryo implantation and indicators of menstrual cycle and fertility, we investigated their role during decidualization. Overall, this study provides an insight into distinct variation in sEV composition depending upon the level of decidualization of endometrial stromal cells, with the signaling potential to coordinate endometrial health ranging from embryo implantation, facilitating placentation and subsequent endometrial regeneration.

2021-11-17 | PXD026342 | Pride

Expression data from bovine conceptus during peri-implantation period

Project description:Conceptus implantation to the uterine endometrium is required for pregnancy establishment, during which non-invasive trophoblasts attach and adhere to the uterine endometrium or invasive trophoblasts invade into the uterine stroma, followed by placental formation in most mammalian species. During peri-implantation period, conceptuses must communicate with the uterine endometrium if they are to survive and proceed to attachment to the uterine epithelium. Despite numerous studies performed on the bovine species, molecular mechanisms associated with their attachment processes, particularly the initial attachment to the endometrial epithelium, have not been well characterized.

2017-12-01 | GSE99654 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data