Endometrial gland impacts on stromal cell decidualization
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE205084 | GEO | 2022/06/06
REPOSITORIES: GEO
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Project description:Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes in gland function across the menstrual cycle are impacted by steroid hormones, estrogen and progesterone, as well as stroma-derived factors. Using an endometrial epithelial organoid (EEO) system, transcriptome and proteome analyses identified distinct responses of the EEO to steroid hormones and prostaglandin E2 (PGE2). Notably, steroid hormones and PGE2 modulated the basolateral secretion of EEO proteins, where cystatin C (CST3) was significantly increased by progesterone and PGE2. CST3 treatment of decidualizing stromal cells significantly decreased the decidualization markers PRL and IGFBP1. The attenuation of stromal cell decidualization via CST3 suggests a role for uterine gland-derived proteins in controlling the extent of decidualization. These findings provide evidence that uterine gland-derived factors directly impact stromal cell decidualization, which has strong implications for better understanding pregnancy establishment and female fertility in humans.
2023-10-11 | PXD034357 | Pride
Project description:A murine model that mimic the decidualization and regression observed in human was used to investigate the molecular mechanisms underlying the dynamic processes in endometrium. Ovariectomized mice were treated sequentially with steroid hormones and then, to induce decidualization, oil was injected into the uterine lumen. A process similar to menstruation was induced by hormone-withdrawal. The uterine tissues were collected at 4 time-points after the induction of decidualization. Keywords: decidualization, menstruation, progesterone-withdrawal, time-course
2006-12-01 | GSE6359 | GEO
Project description:A murine model that mimic the decidualization and regression observed in human was used to investigate the molecular mechanisms underlying the dynamic processes in endometrium. Ovariectomized mice were treated sequentially with steroid hormones and then, to induce decidualization, oil was injected into the uterine lumen. A process similar to menstruation was induced by hormone-withdrawal. The uterine tissues were collected at 4 time-points after the induction of decidualization. Experiment Overall Design: The uterine tissues were collected at 36 (T1), 48 (T2), 60 (T3) and 84 hours (T4) after the last progesterone injection. There are 4 experimental animals for each time-point, and the RNAs collected from animals within the same time-point group were pooled together for Affymetrix microarray analysis using U74Av2 Chips.
2008-06-14 | E-GEOD-6359 | biostudies-arrayexpress
Project description:Implantation of an embryo in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands and receptors are expressed in the pregnant uterus, and BMP2 has been shown to be a key regulator of implantation. In this study, we investigated the roles of the BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy by producing uterine-specific Alk2 conditional knockout (cKO) mice. In the absence of ALK2, embryos can invade the uterine epithelium and stroma, but stromal cells cannot undergo uterine decidualization, resulting in sterility. Mechanistically, microarray analysis revealed that CCAAT/enhancer-binding protein β (Cebpb) expression is suppressed during decidualization in Alk2 cKO females. These findings and the similar phenotypes of Cebpb cKO and Alk2 cKO mice lead to the hypothesis that BMPs act upstream of C/EBPβ to regulate decidualization. To test this hypothesis, we knocked down ALK2 in human uterine stromal cells (HESC) and discovered that ablation of ALK2 alters HESC decidualization and suppresses CEBPB mRNA and protein levels. Chromatin immunoprecipitation (ChIP) analysis of decidualizing HESC confirmed that BMP signaling protein, SMAD1, directly regulates expression of CEBPB by binding a distinct regulatory sequence in the CEBPB promoter; C/EBPβ, in turn, regulates the expression of progesterone receptor (PGR). Our work clarifies the conserved mechanisms through which BMPs regulate embryo implantation in rodents and primates and, for the first time, uncovers a linear pathwayof BMP signaling through ALK2 to regulate CEBPB and, subsequently, PGR during decidualization. gene expression profiling of two groups: control mice and Alk2 cKO mice
2014-01-07 | E-GEOD-46689 | biostudies-arrayexpress
Project description:Ovarian estrogen (E2) and progesterone (P4) are indispensable for embryo-implantation and endometrial stromal decidualization; however, the molecular mechanisms that underpin these reproductive processes are unclear. Steroid receptor coregulator-2 (SRC-2) belongs to the multifunctional SRC/p160 family which also includes SRC-1 and SRC-3. Sharing strong sequence homology, all three SRCs exert diverse regulatory effects by modulating the transcriptional potency of nuclear receptor family members, including the estrogen and progesterone receptor (ER and PR respectively). Importantly, absence of SRC-2 in PR positive cells in the epithelial, stromal, and myometrial compartments of the murine uterus results in a striking infertility defect. This reproductive phenotype highlights a key role for SRC-2 in uterine function which is not shared with other coregulators. Intriguingly, abrogation of uterine SRC-2 does not block embryo apposition or attachment to the apical surface of luminal epithelial cells of the endometrium but rather prevents P4-dependent local decidualization of the sub-epithelial stroma. Remarkably, epithelial-specific ablation of SRC-2 in the murine uterus does not compromise endometrial functionality, again underscoring the unique importance of stromal derived SRC-2 in uterine function. The stromal decidualization defect resulting from SRC-2 ablation is reflected at the molecular level by a marked attenuation in P4 responsive target genes known to be critical for P4 dependent decidualization (i.e. ERBB receptor feedback inhibitor 1, Follistatin and Fkbp5). Conversely, the induction of E2 or P4 target genes involved in embryo implantation (i.e. leukemia inhibitory factor (LIF) and Indian hedgehog (Ihh) respectively) is not affected by SRC-2’s absence. As with mouse studies, decidualization of primary human stromal cells (HESCs) in culture is blocked by SRC-2 knockdown; however, HESC decidualization is unaffected by knockdown of SRC-1 or SRC-3. As a consequence of SRC-2 knockdown, molecular studies disclose a striking decrease in the induction of a subset of P4 target genes (i.e. WNT4 and FKBP5) which are essential for the stromal-epithelioid transformation step, the cellular hallmark of endometrial decidualization. Collectively, these studies not only showcase the evolutionary importance of SRC-2 in endometrial biology but also suggest that deregulation of this coregulator may underpin a spectrum of hormone-dependent uterine pathologies such as endometriosis and endometrial cancer. Microarray analysis was performed on mouse uteri using eighteen SRC-2flox/flox (SRC-2f/f) and eighteen PRCre/+ SRC-2flox/flox (SRC-2d/d) mice. Mice were ovariectomized at 6 weeks and after 2 weeks mice were either treated with sesame oil (vehicle) or 1 mg of P4. RNA from three mice per genotype per treatment were pooled and assigned as one sample (three samples per genotype per treatment). multiple group comparison
2014-04-01 | E-GEOD-31406 | biostudies-arrayexpress
Project description:Implantation of an embryo in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands and receptors are expressed in the pregnant uterus, and BMP2 has been shown to be a key regulator of implantation. In this study, we investigated the roles of the BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy by producing uterine-specific Alk2 conditional knockout (cKO) mice. In the absence of ALK2, embryos can invade the uterine epithelium and stroma, but stromal cells cannot undergo uterine decidualization, resulting in sterility. Mechanistically, microarray analysis revealed that CCAAT/enhancer-binding protein β (Cebpb) expression is suppressed during decidualization in Alk2 cKO females. These findings and the similar phenotypes of Cebpb cKO and Alk2 cKO mice lead to the hypothesis that BMPs act upstream of C/EBPβ to regulate decidualization. To test this hypothesis, we knocked down ALK2 in human uterine stromal cells (HESC) and discovered that ablation of ALK2 alters HESC decidualization and suppresses CEBPB mRNA and protein levels. Chromatin immunoprecipitation (ChIP) analysis of decidualizing HESC confirmed that BMP signaling protein, SMAD1, directly regulates expression of CEBPB by binding a distinct regulatory sequence in the CEBPB promoter; C/EBPβ, in turn, regulates the expression of progesterone receptor (PGR). Our work clarifies the conserved mechanisms through which BMPs regulate embryo implantation in rodents and primates and, for the first time, uncovers a linear pathwayof BMP signaling through ALK2 to regulate CEBPB and, subsequently, PGR during decidualization.
2014-01-07 | GSE46689 | GEO
Project description:Ovarian estrogen (E2) and progesterone (P4) are indispensable for embryo-implantation and endometrial stromal decidualization; however, the molecular mechanisms that underpin these reproductive processes are unclear. Steroid receptor coregulator-2 (SRC-2) belongs to the multifunctional SRC/p160 family which also includes SRC-1 and SRC-3. Sharing strong sequence homology, all three SRCs exert diverse regulatory effects by modulating the transcriptional potency of nuclear receptor family members, including the estrogen and progesterone receptor (ER and PR respectively). Importantly, absence of SRC-2 in PR positive cells in the epithelial, stromal, and myometrial compartments of the murine uterus results in a striking infertility defect. This reproductive phenotype highlights a key role for SRC-2 in uterine function which is not shared with other coregulators. Intriguingly, abrogation of uterine SRC-2 does not block embryo apposition or attachment to the apical surface of luminal epithelial cells of the endometrium but rather prevents P4-dependent local decidualization of the sub-epithelial stroma. Remarkably, epithelial-specific ablation of SRC-2 in the murine uterus does not compromise endometrial functionality, again underscoring the unique importance of stromal derived SRC-2 in uterine function. The stromal decidualization defect resulting from SRC-2 ablation is reflected at the molecular level by a marked attenuation in P4 responsive target genes known to be critical for P4 dependent decidualization (i.e. ERBB receptor feedback inhibitor 1, Follistatin and Fkbp5). Conversely, the induction of E2 or P4 target genes involved in embryo implantation (i.e. leukemia inhibitory factor (LIF) and Indian hedgehog (Ihh) respectively) is not affected by SRC-2’s absence. As with mouse studies, decidualization of primary human stromal cells (HESCs) in culture is blocked by SRC-2 knockdown; however, HESC decidualization is unaffected by knockdown of SRC-1 or SRC-3. As a consequence of SRC-2 knockdown, molecular studies disclose a striking decrease in the induction of a subset of P4 target genes (i.e. WNT4 and FKBP5) which are essential for the stromal-epithelioid transformation step, the cellular hallmark of endometrial decidualization. Collectively, these studies not only showcase the evolutionary importance of SRC-2 in endometrial biology but also suggest that deregulation of this coregulator may underpin a spectrum of hormone-dependent uterine pathologies such as endometriosis and endometrial cancer.
2014-04-01 | GSE31406 | GEO
Project description:It is hypothesized that impaired endometrial decidualization contributes to decreased fertility in endometriosis patients. To identify the molecular defects that underpin defective decidualization in endometriosis, we subjected endometrial stromal cells from healthy individuals or with endometriosis to time course in vitro decidualization with estradiol, progesterone, and 8-bromo-cyclic-AMP (EPC) for 2, 4, 6, or 8 days. Transcriptomic profiling identified novel differences in key pathways between normal and endometriosis, including defective bone morphogenetic protein (BMP) signaling (ID1, ID2, ID3, BMP6), altered iron transport (SLC40A1, TFRC), endometrial stem cell markers (CD44, SUSD2), and retinoid signaling pathways (RORB, ALDH1L1, RARA). Genome-wide binding analyses identified an altered genomic distribution of SMAD4 in decidualized stromal cells from endometriosis patients relative to normal individuals, with an overrepresentation of gene ontologies related to signaling by transforming growth factor β (TGFβ), neurotrophic tyrosine kinase receptors (NTRK), and nerve growth factor (NGF)-stimulated transcription. We found that direct SMAD1/5/4 target genes control FOXO, PI3K/AKT, and progesterone-mediated signaling in decidualizing cells and that BMP2 supplementation of patient-derived assembloids from endometriosis patients restored decidualization. In summary, transcriptomic and genomic profiling of patient-derived endometrial cells and assembloids identified that restoring BMP/SMAD1/5/4 signaling is crucial for engaging a robust decidualization program in women with endometriosis.
2024-02-17 | GSE243157 | GEO
Project description:It is hypothesized that impaired endometrial decidualization contributes to decreased fertility in endometriosis patients. To identify the molecular defects that underpin defective decidualization in endometriosis, we subjected endometrial stromal cells from healthy individuals or with endometriosis to time course in vitro decidualization with estradiol, progesterone, and 8-bromo-cyclic-AMP (EPC) for 2, 4, 6, or 8 days. Transcriptomic profiling identified novel differences in key pathways between normal and endometriosis, including defective bone morphogenetic protein (BMP) signaling (ID1, ID2, ID3, BMP6), altered iron transport (SLC40A1, TFRC), endometrial stem cell markers (CD44, SUSD2), and retinoid signaling pathways (RORB, ALDH1L1, RARA). Genome-wide binding analyses identified an altered genomic distribution of SMAD4 in decidualized stromal cells from endometriosis patients relative to normal individuals, with an overrepresentation of gene ontologies related to signaling by transforming growth factor β (TGFβ), neurotrophic tyrosine kinase receptors (NTRK), and nerve growth factor (NGF)-stimulated transcription. We found that direct SMAD1/5/4 target genes control FOXO, PI3K/AKT, and progesterone-mediated signaling in decidualizing cells and that BMP2 supplementation of patient-derived assembloids from endometriosis patients restored decidualization. In summary, transcriptomic and genomic profiling of patient-derived endometrial cells and assembloids identified that restoring BMP/SMAD1/5/4 signaling is crucial for engaging a robust decidualization program in women with endometriosis.
2024-02-17 | GSE243156 | GEO
Project description:It is hypothesized that impaired endometrial decidualization contributes to decreased fertility in endometriosis patients. To identify the molecular defects that underpin defective decidualization in endometriosis, we subjected endometrial stromal cells from healthy individuals or with endometriosis to time course in vitro decidualization with estradiol, progesterone, and 8-bromo-cyclic-AMP (EPC) for 2, 4, 6, or 8 days. Transcriptomic profiling identified novel differences in key pathways between normal and endometriosis, including defective bone morphogenetic protein (BMP) signaling (ID1, ID2, ID3, BMP6), altered iron transport (SLC40A1, TFRC), endometrial stem cell markers (CD44, SUSD2), and retinoid signaling pathways (RORB, ALDH1L1, RARA). Genome-wide binding analyses identified an altered genomic distribution of SMAD4 in decidualized stromal cells from endometriosis patients relative to normal individuals, with an overrepresentation of gene ontologies related to signaling by transforming growth factor β (TGFβ), neurotrophic tyrosine kinase receptors (NTRK), and nerve growth factor (NGF)-stimulated transcription. We found that direct SMAD1/5/4 target genes control FOXO, PI3K/AKT, and progesterone-mediated signaling in decidualizing cells and that BMP2 supplementation of patient-derived assembloids from endometriosis patients restored decidualization. In summary, transcriptomic and genomic profiling of patient-derived endometrial cells and assembloids identified that restoring BMP/SMAD1/5/4 signaling is crucial for engaging a robust decidualization program in women with endometriosis.
2024-02-17 | GSE243039 | GEO