Uterine epithelial Gp130 orchestrates hormone response and epithelial remodeling for successful embryo attachment in mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA903793 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22355100.fastq.gz | Fastqsanger.gz | |||
| SRR22355101.fastq.gz | Fastqsanger.gz | |||
| SRR22355102.fastq.gz | Fastqsanger.gz | |||
| SRR22355103.fastq.gz | Fastqsanger.gz | |||
| SRR22355104.fastq.gz | Fastqsanger.gz |
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Project description:To investigate the molecular mechanism underlying Gp130-mediated LIF signaling in the endometrium during embryo implantation, we generated mice with uterine epithelium-specific deletion of Gp130. We report the sequencing of the uterine transcriptome of control and uterine epithelium-specific Gp130-deficient mice at day 4 (1600h) of pregnancy.
2023-01-14 | GSE218405 | GEO
Project description:Leukemia inhibitory factor (LIF) receptor, an interleukin 6 cytokine family signal transducer (Il6st, also known as Gp130) that is expressed in the uterine epithelium and stroma, has been recognized to play an essential role in embryo implantation. However, the molecular mechanism underlying Gp130-mediated LIF signaling in the uterine epithelium during embryo implantation has not been elucidated. In this study, we generated mice with uterine epithelium specific deletion of Gp130 (Gp130 ecKO). Gp130 ecKO females were infertile due to the failure of embryo attachment and decidualization. Histomorphological observation revealed that the endometrial shape and embryo position from Gp130 ecKO were comparable to those of the control, and uterine epithelial cell proliferation, whose attenuation is essential for embryo implantation, was controlled in Gp130 ecKO. Comprehensive gene expression analysis using RNA-seq indicates that epithelial Gp130 regulates the expression of estrogen- and progesterone-responsive genes in conjunction with immune response during embryo implantation. We also found that an epithelial remodeling factor, snail family transcriptional repressor 1 (Snai1), was markedly reduced in the pre-implantation uterus from Gp130 ecKO. These results suggest that not only the suppression of uterine epithelial cell proliferation, but also Gp130-mediated epithelial remodeling is required for successful implantation in mice.
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Project description:The objective of the present investigation was to utilize the GeneChip® Porcine Genome Array from Affymetrix possessing 20, 201 unique probe sets to identify differentially expressed genes during rapid trophoblastic elongation and attachment to the uterine surface in the pig. Identification and characterization of conceptus gene expression patterns during rapid trophoblastic elongation and attachment in the pig will provide a better understanding of the events required for successful implantation and embryonic survival.
2008-09-10 | GSE12705 | GEO
Project description:Embryo implantation into a receptive endometrium is tightly regulated by a variety of maternal factors, including cytokines, growth factors and transcription factors. Previous studies identified the leukaemia inhibitory factor (LIF), produced in uterine glands, as an essential factor for implantation. It was shown that LIF acts via its cell surface receptor to activate the transcription factor STAT3 in the uterine epithelial cells. However, the mechanisms via which STAT3 promotes uterine receptivity remain unknown. To address the molecular pathways regulated by STAT3 in the uterus, we created mice in which Stat3 gene is conditionally inactivated in uterine epithelium. These mutant mice are infertile due to implantation failure and exhibit a lack of embryo attachment to the luminal epithelium. Gene expression profiling of the epithelial tissue impaired in STAT3 activation revealed dysregulated expression of specific components of junctional complexes, including E-cadherin, M-NM-2-catenin, and claudins, which critically regulate epithelial cell polarity and embryo attachment. Additionally, mice lacking functional epithelial STAT3 showed markedly reduced stromal proliferation and differentiation, indicating that this transcription factor controls stromal function via a paracrine mechanism. The stromal defect arose from a drastic reduction in the production of several members of the epidermal growth factor (EGF) family in luminal epithelium of mutant uteri and consequent lack of activation of EGF receptor signaling and mitotic activity in the stromal cells. Collectively, our results uncovered intricate signaling networks operating downstream of STAT3 in uterine epithelium that regulate epithelial cell polarity, and stromal proliferation and differentiation, which are critical determinants of successful implantation. To identify the downstream targets of STAT3 in mouse uterine epithelial cells during pregnancy, we performed gene expression profling of mouse uterine epithelial cells on day 4 of pregnancy between Stat3 flox control and SW d/d mice. This led to the identification of several junctional molecules (Claudins and Catenins) that are negatively regulated by STAT3 at the time of implantation. Mouse uteirne epithelial cells were isolated from control and knockout mice on the morning of day 4 of pregnancy. (n=3 for each sample), pooled total RNA from these cells was then hybridized to high density affymetrix microarrays according to the Affymetrix protocol (Mouse Genome 430A 2.0 Array) .
2013-07-01 | E-GEOD-44087 | biostudies-arrayexpress
Project description:Uterine epithelial ERα regulates preimplantation uterine luminal epithelial (LE) and uterine mRNAs
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Project description:Embryo implantation into a receptive endometrium is tightly regulated by a variety of maternal factors, including cytokines, growth factors and transcription factors. Previous studies identified the leukaemia inhibitory factor (LIF), produced in uterine glands, as an essential factor for implantation. It was shown that LIF acts via its cell surface receptor to activate the transcription factor STAT3 in the uterine epithelial cells. However, the mechanisms via which STAT3 promotes uterine receptivity remain unknown. To address the molecular pathways regulated by STAT3 in the uterus, we created mice in which Stat3 gene is conditionally inactivated in uterine epithelium. These mutant mice are infertile due to implantation failure and exhibit a lack of embryo attachment to the luminal epithelium. Gene expression profiling of the epithelial tissue impaired in STAT3 activation revealed dysregulated expression of specific components of junctional complexes, including E-cadherin, β-catenin, and claudins, which critically regulate epithelial cell polarity and embryo attachment. Additionally, mice lacking functional epithelial STAT3 showed markedly reduced stromal proliferation and differentiation, indicating that this transcription factor controls stromal function via a paracrine mechanism. The stromal defect arose from a drastic reduction in the production of several members of the epidermal growth factor (EGF) family in luminal epithelium of mutant uteri and consequent lack of activation of EGF receptor signaling and mitotic activity in the stromal cells. Collectively, our results uncovered intricate signaling networks operating downstream of STAT3 in uterine epithelium that regulate epithelial cell polarity, and stromal proliferation and differentiation, which are critical determinants of successful implantation. To identify the downstream targets of STAT3 in mouse uterine epithelial cells during pregnancy, we performed gene expression profling of mouse uterine epithelial cells on day 4 of pregnancy between Stat3 flox control and SW d/d mice. This led to the identification of several junctional molecules (Claudins and Catenins) that are negatively regulated by STAT3 at the time of implantation.
2013-07-01 | GSE44087 | GEO
Project description:The objective of the present investigation was to utilize the GeneChip® Porcine Genome Array from Affymetrix possessing 20, 201 unique probe sets to identify differentially expressed genes during rapid trophoblastic elongation and attachment to the uterine surface in the pig. Identification and characterization of conceptus gene expression patterns during rapid trophoblastic elongation and attachment in the pig will provide a better understanding of the events required for successful implantation and embryonic survival. Experiment Overall Design: Four chips were used for each morphological stage of development (spherical, tubular, Day 12 filamentous and Day 14 filamentous). RNA utilized for each chip represented a unique pool of conceptus total RNA for the respective morphological stage of development. Prior to target labeling, RNA was further purified (RNeasy MinElute Cleanup, Qiagen, Valencia, CA). Target labeling, GeneChip® hybridization, scanning and quantification were conducted by The University of Tulsa Microarray Core Facility. Affymetrix GeneChip Operating Software (GCOS version 1.1.1, Affymetrix, Santa Clara, CA) was used to quantitate each GeneChip®. The summary intensities for each probe were loaded into DNA-Chip Analyzer (dChip), version 1.3 for normalization, standardization, and analysis.
2008-10-25 | E-GEOD-12705 | biostudies-arrayexpress
Project description:Uterine epithelial estrogen receptor α (ERα) deficiency in epiERα-/- (Esr1f/-Wnt7aCre/+) mice leads to dysregulated environment of uterine lumen, which is lined by uterine luminal epithelium (LE). We hypothesized that LE transcriptomes held molecular keys to understanding ERα in regulating preimplantation uterine environment. Day 0.5 post-coitum (D0.5) and D3.5 LE (isolated via enzymatic digestion), digested uterus (DU), and flash-frozen uterus (U) from Esr1f/- (control) and epiERα-/- mice were processed for mRNA-seq. There were minimal differentially expressed genes (DEGs, TPM>1, FC>2, FDR<0.05) between DU and U. Between D0.5 and D3.5 Esr1f/- LE, the top upregulated and downregulated GOBP pathways were on cellular processes and on innate immune responses, respectively, with the later also seen in Esr1f/- U. Compared to Esr1f/- LE, the most upregulated and downregulated pathways in D0.5 epiERα-/- LE were on innate immune responses and on biosynthesis and metabolism, respectively; while those in D3.5 epiERα-/- LE were on cell division and on signaling and metabolic processes, respectively. Na+ transmembrane transport was among shared upregulated pathways in D0.5 and D3.5 epiERα-/- LE. Between Esr1f/- and epiERα-/-, most DEGs in U were also DEGs in LE, limited DEGs in U only with higher expression than in LE were related to immune responses, implicating potential paracrine effects of uterine epithelial ERα. Selected DEGs were verified by realtime PCR and immunohistochemistry. This mRNA-seq dataset provides molecular keys to understanding temporal (e.g., innate immunity) and constituent (e.g., uterine fluid movement) functions, and potential paracrine effects of uterine epithelial ERα in regulating the preimplantation uterine environment.
2025-12-01 | GSE311705 | GEO
Project description:Uterine adaptations driven by the steroid hormones estrogen and progesterone are pivotal for embryo implantation and, ultimately for a successful pregnancy. Here, we show that genetic ablation of the membrane lipid flippase Atp11a in mice causes severe deficits in this hormonal response and profound defects in the morphological organization and transcriptional profile of the uterine epithelial compartment where ATP11A is expressed. Atp11a-null uterine epithelial cells lack tight junctions, and the luminal epithelium exhibits profound disruptions to cellular morphology as it displays a loss of the columnar epithelial architecture and instead acquires a multi-layered morphology of rounded cells resembling a squamous epithelium. Furthermore, the specification of luminal epithelial cells remains incomplete as they maintain expression of the normally gland-restricted marker FOXA2. The uterine glands of Atp11a-null females are depleted for progenitor cells marked by SOX9, PAX8, LGR5 and PROM1. Collectively, these defects likely underpin the frequent early pregnancy losses in Atp11a-depleted females. Most intriguingly, however, loss of only a single functional Atp11a allele causes a higher frequency of abnormal placental trophoblast differentiation as well as a higher incidence of congenital heart defects in wild-type embryos. These data highlight the far-reaching impact of uterine dysfunction on reproductive outcome and highlight the importance of the maternal genotype in the etiology of developmental disorders.
2025-04-07 | GSE278900 | GEO
Project description:Uterine receptivity (the window of implantation) is essential for successful implantation. The concept of uterine receptivity was first discovered 50 years ago by Psychoyos. In mice, uterine receptivity begins with the secretion of LIF from uterine glands stimulated by estrogen on the morning of day 4 pregnancies. However, some implantation failure is due to the lack of responses to the estrogen secretion. The current study reveals that uterine glands undergo a differentiation process with increases in more branches during the preimplantation period. The single cell RNA profiling of glandular cells identifies that LIF is expressed exclusively in a Prss29+ subgroup of glands in response to estrogen secretion on day 4 of pregnancy. Previous studies have shown that Foxa2 deficiency in uterine glands results in implantation failure due to lack of LIF production. Interestingly, Foxa2-deficient glands fail to develop branches and the functional Prss29+ subgroup of gland cells, indicating FOXA2 is obligatory for normal glandular differentiation prior to implantation. We found that this group develops by the evening of day 3 of pregnancy prior to estrogen secretion on day 4 mornings. We noticed that Lif mRNA signals are detected in the uterus comprising the Prss29+ subgroup. Our findings indicate that uterine glands undergo a FOXA2-dependent maturation process to acquire the competence, which we have termed the “transitional phase,” necessary to respond to estrogen. This newly identified glandular "transitional phase" represents a landmark concept in the study of uterine receptivity and implantation biology.
2025-02-15 | GSE275806 | GEO