Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148274 | GEO | 2021/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The Extracellular Vesicles Proteome of Endometrial Cells Simulating the Receptive Menstrual Phase Differs from That of Endometrial Cells Simulating the Non-Receptive Menstrual Phase

Project description:Successful embryo implantation into a receptive endometrium requires mutual endometrial-embryo communication. Recently, the function of extracellular vehicles (EVs) in cell-to-cell interaction in embryo-maternal interactions has been investigated. We explored isolated endometrial derived EVs, using RL95-2 cells as a model of a receptive endometrium, influenced by menstrual cycle hormones estrogen (E2; proliferative phase) progesterone (P4; secretory phase) and estrogen plus progesterone (E2P4; the receptive phase). EV sized particles were isolated by differential centrifugation and size exclusion chromatography. Nanoparticle tracking analysis was used to examine the different concentration and size of particles and EV proteomic analysis per-formed using shotgun label-free mass spectrometry. Our results showed that although endome-trial derived EVs were secreted in numbers independent of hormonal stimulation, EVs sizes were statistically modified by it. Proteomics analysis showed that hormone treatment changes affect the endometrial EVs proteome, with proteins enhanced within the EV E2P4 group shown to be in-volved in different processes such as embryo implantation, endometrial receptivity, and embryo development, supporting the concept of a communication system between the embryo and the maternal endometrium via EVs.

2023-02-13 | PXD039764 | Pride

Identification and profiling of microRNAs in goat endometrium during Embryo Implantation

Project description:Our data revealed the first miRNA profile related to the biology of the goat receptive endometrium during embryo implantation. The results suggested that a subset of miRNAs might play important roles in the formation of endometrial receptivity. Thus, elucidating the physiological roles of endometrial miRNAs will help us better understand the genetic control of implantation, which is the gateway to a successful pregnancy.

2017-02-09 | GSE63422 | GEO

Gene expression study of human endometrial receptivity in IVF implantation failure patients undergoing ovarian stimulation II

Project description:Endometrial receptivity on genomic level is one of the major cause of implantation failure in IVF patients with unexplained infertility and is a main obstacle in success of IVF. Gene expression profiles of implantation failure cases of unexplained infertility were compared with proven healthy oocyte donors as controls, both undergoing ovarian stimulation. The results provide additional information about gene expression profile related to endometrial receptivity in implantation failure cases especially under the influence of ovarian stimulation during IVF cycle.

2019-06-25 | GSE92324 | GEO

Gene expression study of human endometrial receptivity in IVF implantation failure patients undergoing ovarian stimulation

Project description:Endometrial receptivity on genomic level is one of the major cause of implantation failure in IVF patients with unexlained infertility and is a main obstacle in success of IVF. Gene expression profiles of implantation failure cases of unexplained infertility were compared with proven healthy oocyte donors as controls, both undergoing ovarian stimulation. The results provide additional information about gene expression profile related to endometrial receptivity in implantation failure cases especially under the influence of ovarian stimulation during IVF cycle.

2018-08-07 | GSE71835 | GEO

Expression profile of early and mid-secretory human endometrium revealed by RNA-seq: a paired-sample cohort study

Project description:Inner uterine lining or endometrium is a unique constantly self-renewed adult tissue that is vital for embryo implantation. As the footrace for universal endometrial receptivity markers continues, RNA-seq remains the most powerful tool for transcriptomic marker discovery. In this study, we aimed to elucidate endometrial maturation mechanisms at transcriptomic level and identify novel robust biomarker candidates for endometrial receptivity in a multicentre study. Additionally, we compared mid-secretory transcriptome profiles from healthy women with profiles of women with repeated IVF failure to find transcriptome changes related to problems with endometrial receptivity.

2020-11-07 | GSE106602 | GEO

Gene expression profiling in periimplantation mouse uterine luminal epithelium

Project description:We used the microarray analysis to determine the differential gene expression profiles in mouse uterine luminal epithelium between preimplantation gestation day 3.5 and postimplantation gestation day 4.5, and investigeate the molecular mechanism of the establishment of uterine receptivity and embryo implantation. Uterine luminal epithelium (LE) is critical for the establishment of uterine receptivity during embryo implantation. Many genes are known to have differential expression in the periimplantation LE but the global profiling of the altered genes in the periimplantation LE is unknown. To fill in this knowledge gap, microarray analysis was performed in gestation day 3.5 (D3.5, preimplantation) and D4.5 (postimplantation) mouse LE from natural pregnancy. There were 382 significantly upregulated and 245 significantly downregulated genes (>2 fold, P<0.05) in the D4.5 LE. There are 6 samples. 3 for gestation day 3.5 uterine luminal epithelium, the other 3 for gestation day 4.5 uterine luminal epithelium

2013-02-25 | E-GEOD-44451 | biostudies-arrayexpress

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

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

| PRJNA623636 | ENA

Increased AIF-1-mediated TNF-α expression during the implantation phase in IVF cycles with GnRH antagonist protocol

Project description:Administration of GnRH antagonist in IVF has several advantages. However, studies have shown that GnRH antagonist protocol cycles have lower implantation and clinical pregnancy rates than GnRH agonist long protocol cycles. Endometrial receptivity rather than embryo quality is thought to account for this phenomenon, however the mechanism is still largely unknown. This microarray analysed human endometrium during ‘implantation window phase’ between three groups: 1) untreated control, 2) GnRH agonist long protocol, and 3) GnRH antagonist protocol. The differential gene between groups uncovered the molecular mechanism occurred in endometrium affected by the intake of GnRH agonist or GnRH antagonist. Further study of these differential gene promises to find the reasons for lower endometrial receptivity in patients treated with GnRH antagonist and to improve the implantation rate in GnRH antagonist protocols in IVF.

2018-06-27 | GSE107914 | GEO

Blastocyst derived signal facilitate the embryo implantation via protein degradation via activating lysosome in the uterine epithelia [RNA-Seq: Epithelium_Igf1r_WT_KO]

Project description:The mammalian endometrium is covered by the luminal epithelium (Le), which directly interacts with the blastocyst and plays an important role in the establishment of reciprocal crosstalk between the embryo and receptive uterus during implantation. However, the effect of the blastocyst on uterine receptivity is far from well understood. Through transcriptomic profiling of the uterine Le isolated by laser capture microdissection, it was demonstrated that global gene expression changes occurred in Le between pseudopregnant mice without embryos and pregnant mice with embryos. Some differentially expressed genes, including upregulated Areg, Ihh, Lifr and downregulated Msx1, Pgr, Gata2, have been reported to regulate the establishment of uterine receptivity. Besides, we found that blastocysts induced an increase in both the number and acidification of lysosome, consistent with enhanced lysosomal hydrolase activity in uterine Le. Further exploration uncovered that blastocyst-derived IGF2 was involved into the activation of epithelial STAT3 to induce lysosomal hydrolase expression, and inhibition of lysosomal function derails normal uterine receptivity and embryo implantation. Finally, based on the proteomic data of both epithelia and the separated lysosome, it was revealed that CLDN1 and MUC1, two well-known downregulated molecules for successful implantation, are degraded by epithelial lysosome. In brief, our data demonstrated that blastocysts induced normal epithelium differentiation with lysosome activation to promote the establishment of uterine receptivity for embryo implantation.

2024-01-10 | GSE231827 | GEO

Blastocyst derived signal facilitate the embryo implantation via protein degradation via activating lysosome in the uterine epithelia [RNA-Seq: Epithelium_D4_PsdD4]

2024-01-10 | GSE231826 | 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