LIFR-mediated ERBB2 signaling is essential for successful embryo implantation in mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE293425 | GEO | 2025/05/12
REPOSITORIES: GEO
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Project description:LIFR-mediated ERBB2 signaling is essential for successful embryo implantation in mice.
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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
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: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 | GSE231826 | GEO
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
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: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:Intrauterine BoTA treatment has a beneficial effect on vascular reconstruction of functional endometrium prior to embryo implantation by increasing endometrial blood flow near the uterine cavity suggesting BoTA treatment as a potential therapeutic strategy for patients who are suffering from repeated implantation failure with the problems with endometrial receptivity.
2021-06-02 | GSE146934 | GEO
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
Project description:Receptivity of the uterus is essential for embryo implantation and progression of pregnancy. Acquisition of receptivity involves major molecular and cellular changes in the endometrial lining of the uterus from its non-receptive state at ovulation, to its receptive state four days later. The precise molecular mechanisms underlying this transition remain to be fully characterized. Here, we aimed to generate a comprehensive profile of the uterine transcriptome in the peri-ovulatory and peri-implantation states, and to define the differences between them, in the mouse. High throughput RNA-sequencing was utilized to identify genes and pathways expressed in the endometrium of C57Bl/6 female mice on day 3.5 post-coitum after mating with BALB/c males, compared to the endometrium of unmated estrous females (n=3-4 biological replicates). RNA-sequencing and analysis using Ingenuity Pathway Analysis software revealed that, compared to the endometrium at estrus, 388 genes were differentially expressed in the endometrium on day 3.5 post-coitum (FDR ≤ 0.05). Several upstream regulators are implicated in the transition to receptivity including several cytokines, steroid hormones, prostaglandin E2, and vascular endothelial growth factor A. The transcriptional changes indicate substantial changes in the uterine immune and vascular systems during the pre-implantation phase, with the functional terms Angiogenesis, Chemotaxis, and Lymphangiogenesis predominating. This analysis confirms that the transcriptome of a receptive uterus is vastly different to the non-receptive uterus and identifies several genes and regulatory pathways not previously associated with implantation. This dataset will serve as a valuable tool and resource for future research on the molecular mechanisms of uterine receptivity.
2023-09-12 | GSE223136 | GEO