DNA methylation dynamics of the human pre-implantation embryo
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ABSTRACT:
PROVIDER: PRJNA221793 | ENA |
REPOSITORIES: ENA
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Project description:We present genome-scale maps of DNA methylation in early human development and perform comparative analysis to mouse that confirm a conserved global erasure of the paternal genome. We find that while many global features of the early embryo are consistent between the two species, the target sequences in which DNA methylation is maintained are distinct. Repetitive elements show a broader range of class specific behaviors in the human embryo and a larger degree of methylation escape in human sperm. We identify thousands of differentially methylated regions (DMRs) that are likely of maternal origin and found that these gamete contributed DMRs are far more species-specific than expected given the conservation of canonical imprint control regions (ICRs). Finally, we extended our studies to the derivation of new human embryonic stem cell (ESC) lines and found notable divergences in DNA methylation signatures from those found in the human embryo and different mouse ESC derivation conditions. Comparison of DNA methylation patterns in human early development, human ESC derivation and mouse ESC derivation
2014-07-23 | E-GEOD-51239 | biostudies-arrayexpress
Project description:Although the landscape of epigenomic and transcriptomic regulation during human pre-implantation development has been depicted by applying single-cell sequencing, the investigation of embryonic proteome is almost unrevealed due to the insufficient input quantity from precious human embryonic samples for traditional mass spectrometry (MS). With applying the state-of-the-art ultrahigh sensitivity mass spectrometry technology and nanoliter-scale oil-air-droplet (OAD) chip, we were able to identify more than three thousand proteins in a single oocytes during human pre-implantation development. Hundreds of stage-specific proteins with significant expressional changes were classified. Many that involve important functions, such as paternal genome reprogramming or DNA methylation, were firstly identified in human embryo studies. We discovered a two peaks of “zygotic proteome activation” (ZPA) at 2-cell and morula stages, in which proteins are mainly associated with epigenetic reprogramming. Our study, for the first time, delineates a comprehensive stage-specific proteome landscape at a single-cell level. It is as well a large step of enriching the panorama of functional genomics across human pre-implantation embryo development.
2021-04-20 | PXD024267 |
Project description:We present genome-scale maps of DNA methylation in early human development and perform comparative analysis to mouse that confirm a conserved global erasure of the paternal genome. We find that while many global features of the early embryo are consistent between the two species, the target sequences in which DNA methylation is maintained are distinct. Repetitive elements show a broader range of class specific behaviors in the human embryo and a larger degree of methylation escape in human sperm. We identify thousands of differentially methylated regions (DMRs) that are likely of maternal origin and found that these gamete contributed DMRs are far more species-specific than expected given the conservation of canonical imprint control regions (ICRs). Finally, we extended our studies to the derivation of new human embryonic stem cell (ESC) lines and found notable divergences in DNA methylation signatures from those found in the human embryo and different mouse ESC derivation conditions.
2014-07-23 | GSE51239 | GEO
Project description:The developmental origins of adult disease are now recognized to reflect intrauterine conditions during embryonic and fetal life. Cell-cell communication between the maternal endometrium and the pre-implantation embryo can occur by several means. Here, we show that maternal miRNAs are secreted by the endometrial epithelium to the endometrial fluid. Microarray assessments revealed the presence of specific miRNAs that are associated with the window of implantation and therefore in direct contact with the human preimplantation embryo. These miRNAS are transported as free or exosome-associated molecules secreted to the endometrial fluid and then uptake into the pre-implantation embryo through the trophoectoderm. Finally, these maternal miRNAsS were able to induce transcriptional and functional modifications of the embryo. Therefore, we propose an innovative model whereby endometrial maternal miRNAS may function as transcriptomic regulators during early embryo development offering a new perspective on the developmental origins of adult diseases such as obesity, type 2 diabetes, and others that are now recognized to reflect intrauterine conditions.
2014-06-02 | GSE44558 | GEO
Project description:The developmental origins of adult disease are now recognized to reflect intrauterine conditions during embryonic and fetal life. Cell-cell communication between the maternal endometrium and the pre-implantation embryo can occur by several means. Here, we show that maternal miRNAs are secreted by the endometrial epithelium to the endometrial fluid. Microarray assessments revealed the presence of specific miRNAs that are associated with the window of implantation and therefore in direct contact with the human preimplantation embryo. These miRNAS are transported as free or exosome-associated molecules secreted to the endometrial fluid and then uptake into the pre-implantation embryo through the trophoectoderm. Finally, these maternal miRNAs were able to induce transcriptional and functional modifications of the embryo. Therefore, we propose an innovative model whereby endometrial maternal miRNAS may function as transcriptomic regulators during early embryo development offering a new perspective on the developmental origins of adult diseases such as obesity, type 2 diabetes, and others that are now recognized to reflect intrauterine conditions.
2014-06-02 | GSE44730 | GEO
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: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:The developmental origins of adult disease are now recognized to reflect intrauterine conditions during embryonic and fetal life. Cell-cell communication between the maternal endometrium and the pre-implantation embryo can occur by several means. Here, we show that maternal miRNAs are secreted by the endometrial epithelium to the endometrial fluid. Microarray assessments revealed the presence of specific miRNAs that are associated with the window of implantation and therefore in direct contact with the human preimplantation embryo. These miRNAS are transported as free or exosome-associated molecules secreted to the endometrial fluid and then uptake into the pre-implantation embryo through the trophoectoderm. Finally, these maternal miRNAsS were able to induce transcriptional and functional modifications of the embryo. Therefore, we propose an innovative model whereby endometrial maternal miRNAS may function as transcriptomic regulators during early embryo development offering a new perspective on the developmental origins of adult diseases such as obesity, type 2 diabetes, and others that are now recognized to reflect intrauterine conditions. This is a prospective study in which endometrial fluid was obtained from healthy patients that had no underlying endometrial pathology and had regular menstrual cycles of between 25 and 33 days. None of these women had received a hormonal preparation in the 3 months preceding biopsy (fluid) collection. Endometrial (fluid) samples were distributed in five groups according to the phase in the cycle: group 1, Early Proliferative (EP) (days 1M-bM-^@M-^S8); group 2, Late Proliferate (LP) (days 9M-bM-^@M-^S14); group 3, Early Secretory (ES) (days 15M-bM-^@M-^S18); group 4, Window of Implantation (WOI) (days 19M-bM-^@M-^S22); and group 5, Late Secretory (LS) (days 23M-bM-^@M-^S28) according to the criteria of Noyes {Noyes:1975vl}. A total of 20 patients were included, four per group
2014-06-02 | E-GEOD-44558 | biostudies-arrayexpress
Project description:Histone modifications play critical roles in regulating developmental genes expression during embryo development in mammals1,2. However, genome-wide analysis of histone modifications in pre-implantation embryos has been impeded by technical difficulties and the scarcity of required materials. Here, by using a small-scale chromatin immunoprecipitation sequencing (ChIP-seq) method3, for the first time, we mapped the genome-wide profile of histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), associated with gene activation and repression respectively, in mouse pre-implantation embryos. We found that the establishment of H3K4me3 mark occurs much more rapidly than that of H3K27me3 following fertilization. Furthermore, H3K4me3 and H3K27me3 possess distinct features in sequence preference and dynamics in pre-implantation embryos. Although most H3K4me3 signature constantly exists on transcription start site (TSS) region, the breadth of H3K4me3 domain is of high-dynamic feature. Interestingly, the broad H3K4me3 peak (wider than 5kb) is associated with higher transcription activity and cell identity not only in pre-implantation embryos but also in the process of deriving embryonic stem cells (ESCs) from the inner cell mass (ICM) and trophoblast stem cells (TSCs) from the trophectoderm (TE). Unlike those observed in ESCs, we found that the bivalency (containing both H3K4me3 and H3K27me3) is unstable and not frequently observed in early cleavage stage embryos until the morula to blastocyst transition. Taken all together, our study provides a genome-wide map of H3K4me3 and H3K27me3 modifications in pre-implantation embryos, which offers us opportunities to further understand the epigenetic regulation mechanism in early embryo development.
2016-09-15 | GSE73952 | GEO
Project description:The developmental origins of adult disease are now recognized to reflect intrauterine conditions during embryonic and fetal life. Cell-cell communication between the maternal endometrium and the pre-implantation embryo can occur by several means. Here, we show that maternal miRNAs are secreted by the endometrial epithelium to the endometrial fluid. Microarray assessments revealed the presence of specific miRNAs that are associated with the window of implantation and therefore in direct contact with the human preimplantation embryo. These miRNAS are transported as free or exosome-associated molecules secreted to the endometrial fluid and then uptake into the pre-implantation embryo through the trophoectoderm. Finally, these maternal miRNAs were able to induce transcriptional and functional modifications of the embryo. Therefore, we propose an innovative model whereby endometrial maternal miRNAS may function as transcriptomic regulators during early embryo development offering a new perspective on the developmental origins of adult diseases such as obesity, type 2 diabetes, and others that are now recognized to reflect intrauterine conditions. The B6C3F1 mice strain was purchased. Female mice aged 6M-bM-^@M-^S8 weeks were primed to ovulate by administering 10 IU pregnant mare serum gonadotropin(Sigma-Aldrich, Irvine, UK), followed by administration of 10 IU hCG(Sigma-Aldrich, Irvine, UK), 48 hours later. Females were housed overnight with male breeders and examined the following morning for the presence of a vaginal plug (day 1 of pregnancy). On day 2 of pregnancy, mice were sacrificed by cervical dislocation, and embryos flushed with PBS from the oviduct using a blunt 30-gauge needle. Then, embryos were cultured in CCM-30 medium (Vitrolife, Lubeck, Germany) in presence or absence of 400nM of mir-30d MIMIC or Scramble-Alexa 488 for 72 hours. Then embryos are four times washed in fresh CCM. Experiment were carried out by triplicate and with 30 embryos/condition
2014-06-02 | E-GEOD-44730 | biostudies-arrayexpress