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Single cell mapping of the human endometrium and first trimester decidua identifies distinct epithelial and stromal cell contributions to fertility [single cell RNA-seq]

ABSTRACT: Embryo implantation relies on the development of a receptive endometrium during the secretory phase of the menstrual cycle. Prior studies have attempted to define the window of embryo implantation within the secretory phase based on patterns of differentially expressed genes, but consensus surrounding this signature has not been achieved. We aim to examine the cell types that characterize the purported receptivity signature and identify new transcriptomic markers that define the mid-secretory endometrium through integrated bulk and single-cell RNA sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290822 | GEO | 2025/11/24

REPOSITORIES: GEO

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Decoding the endometrial landscape at single-cell resolution from implantation preparation to early pregnancy [bulk RNA-seq]

Project description:Embryo implantation relies on the development of a receptive endometrium during the secretory phase of the menstrual cycle. Prior studies have attempted to define the window of embryo implantation within the secretory phase based on patterns of differentially expressed genes, but consensus surrounding this signature has not been achieved. We aim to examine the cell types that characterize the purported receptivity signature and identify new transcriptomic markers that define the mid-secretory endometrium through integrated bulk and single-cell RNA sequencing.

2025-11-24 | GSE289073 | GEO

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

A bovine 3D endometrium-on-a-chip reveals the role of conceptus-derived factors CAPG and PDI in conceptus-endometrial communication

Project description:Early embryo loss affects all mammalian species, including humans and agriculturally important food-producing mammals such as cattle. The developing conceptus (embryo and extra-embryonic membranes) secretes factors which modify the endometrium and can be critical for early pregnancy processes such maternal recognition of pregnancy (MRP) and enhancing uterine receptivity to implantation. For example, a competent bovine conceptus secretes IFNT to initiate MRP. The bovine conceptus also secretes other proteins at the time of MRP, including CAPG and PDI, which are highly conserved among placental mammals. We have previously shown that these proteins act upon the endometrium to modulate receptivity, embryo development, and implantation in species with different implantation strategies (humans and cattle). We hypothesise that developing a novel 3D bovine endometrium on a chip system will enhance our understanding of the role of conceptus-derived factors in altering the endometrium and/or ULF secretion. Here we have developed a 3D bovine endometrium on a chip system, comprising both stromal and epithelial cell culture combined with culture medium flow better mimics the in vivo endometrium and exposure to conceptus-derived factors than conventional 2D endometrial cell culture. We have demonstrated that the conceptus-derived proteins CAPG and PDI modulate the endometrial transcriptome and secretory response to promote pathways associated with early pregnancy and alter ULF composition. This work highlights the critical need for more robust and in vivo-like culture systems to study endometrial-conceptus interactions in vitro to further investigate the role of conceptus derived factors for pregnancy success.

2025-05-19 | PXD059725 | 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.

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Transcriptional profiling of healthy versus cystic fibrosis human endometrial organoids upon hormonal exposure

Project description:Female cystic fibrosis (CF) patients are confronted with fertility deficiency, experiencing difficulties in getting pregnant. Underlying reasons remain elusive. In particular, it has only poorly been studied whether the endometrium, the inner lining of the womb and crucial tissue for embryo implantation, plays a role. One main reason is the lack of reliable and tractable study models given the major technical and ethical hurdles to study events that occur hidden in the womb.To overcome this, we established an endometrium CF organoid model. We applied bulk RNA sequencing on these organoids derived form endometrium of women affected by CF and of healthy women. These endometrial organoids (EO) were exposed to hormones to mimic different phases of the menstrual cycle. The proliferative phase was mimicked by exposing the EO to estradiol (+E2), while the (mid-)secretory phase was mimicked by estradiol, progesterone, cyclic AMP and XAV-939 (Wnt inhibitor) (EPCX) exposure of EO. As a control, we sequenced healthy and CF EO not exposed to hormones (EOM).

2025-04-08 | E-MTAB-14456 | biostudies-arrayexpress

Gene expression in mouse uterus during pre-implantation period after intrauterine administration treatment

Project description:Intrauterine peripheral blood mononuclear cells (PBMC) therapy for recurrent implantation failure (RIF) has been reported to improve embryo implantation by acting on the endometrium. However, the exact mode of action of PBMC on the endometrium and the differences in the therapeutic effects of PBMC therapy with and without human chorionic gonadotropin (hCG) are unknown. In this study, we investigated the changes in the endometrium during the implantation phase induced by PBMC administration and the differences in the efficacy of this therapy with and without hCG using a mouse model of implantation failure (IF).

2024-12-09 | GSE280930 | GEO

Proteomic profiles of endometrium during embryo implantation

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

Transcription profiling of human endometrium from patients with a history of endometriosis vs. normal controls sampled at a range of menstrual cycle timepoints reveals progesterone resistance and candidate susceptibility genes in women with endometriosis

Project description:The transition of regularly cycling endometrium from the proliferative or Estrogen-dominant phase of the menstrual cycle to the Progesterone-dominant Early and Mid Secretory phases requires wide-spread changes in gene expression that shift the endometrium from a proliferative capacity to a differentiated 'decidual' phenotype in preparation for implantation. This process appears delayed in women with severe endometriosis, suggestive of a progesterone resistant endometrium in this disease. Experiment Overall Design: Endometrial biopsies were obtained from women both with normal endometrial pathologies and no history of endometriosis and from women with laporoscopy proven moderate-severe stage endometriosis. Samples were collected from the Proliferative(PE), Early Secretory (ESE) and Midsecretory (MSE) phases. Samples were then processed for Total RNA isolation and Affymetrix chip hybridization.

2008-04-09 | E-GEOD-6364 | biostudies-arrayexpress

Gene Profiling of Endometrium Reveals Progesterone Resistance and Candidate Genetic Loci in Women with Endometriosis

2007-05-01 | GSE6364 | GEO

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

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