Extracellular vesicles from human Fallopian tubal fluid benefit embryo development in vitro
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA934056 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23426200.fastq.gz | Fastqsanger.gz | |||
| SRR23426201.fastq.gz | Fastqsanger.gz | |||
| SRR23426202.fastq.gz | Fastqsanger.gz | |||
| SRR23426203.fastq.gz | Fastqsanger.gz | |||
| SRR23426204.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:STUDY QUESTION: Do extracellular vesicles (EVs) from human Fallopian tubes exert an influence on early embryo development in vitro? SUMMARY ANSWER: Human Fallopian tube EVs carrying miRNAs increase murine embryo viability in vitro. WHAT IS KNOWN ALREADY: Oviductal EVs (oEVs) are recently identified key players in embryo-oviduct interactions that contribute to successful pregnancy in vivo. Their absence in current in vitro systems may partly explain the suboptimal embryo development observed, therefore further knowledge is needed about their impact on early embryos. STUDY DESIGN, SIZE, DURATION: The oEVs were isolated from the luminal fluid of human Fallopian tubes using ultracentrifugation. We cocultured oEVs with murine two-cell embryos until the blastocyst stage. The study was conducted between August 2021 and July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 23 premenopausal women were recruited for Fallopian-tubes collection, and the oEVs were isolated. The micro RNA (miRNA) contents were detected using high-throughput sequencing and their target genes and effects were analyzed. After in vitro culture with or without oEVs, the blastocyst and hatching rates were recorded. Furthermore, for the blastocysts formed, we assessed the total cell number, inner cell mass proportion, reactive oxygen species (ROS) level, number of apoptotic cells and mRNA expression levels of genes involved in development. MAIN RESULTS AND THE ROLE OF CHANCE: EVs were successfully isolated from the human Fallopian tubal fluid and the concentrations were evaluated. A total of 79 known miRNAs were identified from eight samples that had been sequenced, all involved in various biological processes. The blastocyst rate, hatching rate, as well as total cell number of blastocysts were significantly increased in the oEVs-treated groups (p < 0.05 versus untreated), while the proportion of inner cell mass showed no significant difference between groups. ROS levels and apoptotic cell proportions were decreased in the oEVs-treated groups (p < 0.05 versus untreated). The genes, Actin-Related Protein 3 (Actr3), Eomesodermin (Eomes), and Wnt Family Member 3A (Wnt3a) were upregulated in blastocysts in the oEVs-treated group.
2023-02-16 | GSE225122 | GEO
Project description:Study questionDo extracellular vesicles (EVs) from human Fallopian tubes exert an influence on early embryo development in vitro?Summary answerHuman Fallopian tube EVs carrying miRNAs increase murine embryo viability in vitro.What is known alreadyOviductal EVs (oEVs) are recently identified key players in embryo-oviduct interactions that contribute to successful pregnancy in vivo. Their absence in current in vitro systems may partly explain the suboptimal embryo development observed; therefore, further knowledge is needed about their impact on early embryos.Study design size durationThe oEVs were isolated from the luminal fluid of human Fallopian tubes using ultracentrifugation. We cocultured oEVs with murine two-cell embryos until the blastocyst stage. The study was conducted between August 2021 and July 2022.Participants/materials setting methodsA total of 23 premenopausal women were recruited for Fallopian-tubes collection, and the oEVs were isolated. The micro RNA (miRNA) contents were detected using high-throughput sequencing and their target genes and effects were analyzed. After in vitro culture with or without oEVs, the blastocyst and hatching rates were recorded. Furthermore, for the blastocysts formed, we assessed the total cell number, inner cell mass proportion, reactive oxygen species (ROS) level, number of apoptotic cells, and mRNA expression levels of genes involved in development.Main results and the role of chanceEVs were successfully isolated from the human Fallopian tubal fluid and the concentrations were evaluated. A total of 79 known miRNAs were identified from eight samples that had been sequenced, all involved in various biological processes. The blastocyst rate, hatching rate, as well as total cell number of blastocysts were significantly increased in the oEVs-treated groups (P < 0.05 versus untreated), while the proportion of inner cell mass showed no significant difference between groups. ROS levels and apoptotic cell proportions were decreased in the oEVs-treated groups (P < 0.05 versus untreated). The genes, Actr3 (actin-related protein 3), Eomes (eomesodermin), and Wnt3a (Wnt family member 3A) were upregulated in blastocysts in the oEVs-treated group.Large scale dataData are available from Gene Expression Omnibus: Accession number: GSE225122.Limitations reasons for cautionThe Fallopian tubes in the current study were collected from patients with uterine fibroids (the reason they underwent hysterectomy), and this pathological condition may affect the characteristics of EVs in luminal fluid. Also, owing to restrictions for ethical reasons, an in vitro co-culture system using murine embryos was used instead of human embryos, and the findings may not be transferable.Wider implications of the findingsDeciphering miRNA contents in human oEVs and providing new evidence that oEVs benefit embryo development in vitro will not only increase our knowledge on embryo-oviduct communication but also potentially improve ART outcomes.Study funding/competing interestsThis study was supported by the National Key Research and Development Project of China (2021YFC2700603). No competing interests are declared.
| S-EPMC9991590 | biostudies-literature
Project description:Endometriosis (EM) is a well-recognized disease that causes infertility in women of reproductive age. Tubal EM adversely affects fallopian tube function and female reproductive outcomes. Our study aimed to evaluate the effect of tubal EM on tubal epithelial ultrastructure and to explore the possible mechanisms of tubal infertility by analyzing the differential expression of exosomal microRNAs (miRNAs) in tubal fluid. We obtained human fallopian tube epithelium and tubal fluid samples from patients with and without tubal EM. We used scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to assess ultrastructural changes. Exosomal miRNAs in tubal fluid were extracted for microarray. We visualized epithelial damage in the tubal EM group using electron microscopy. The number of organelles decreased, and organelle structure was destroyed. A total of 14 differentially expressed exosomal miRNAs were detected in tubal fluid (fold change >2 and P value <0.05). Four miRNAs (miR-1273f, miR-5699-5p, miR-6087, miR-6747-5p) were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatic analysis showed that most of the target genes participated in embryo transport, regulation of cell communication, anatomical structure morphogenesis, and immune system processes. We verified that tubal EM damaged the tubal epithelial ultrastructure in human specimens and identified differentially expressed exosomal miRNAs in tubal liquid. These findings may elucidate the pathogenesis of tubal EM-associated infertility.
2023-06-22 | GSE220787 | GEO
Project description:Serous tubal intraepithelial carcinomas (STIC lesions) in the human fallopian tube epithelium (hFTE) are theorized to give rise to high grade serous ovarian cancers (HGSOC). Small extracellular vesicles (sEVs) are known to mediate key signaling in both normal and cancerous tissues, but few ex vivo systems exist for studying sEV impact on hFTE tissue. Here, we present a microfluidic tissue culture platform with combined spatial transcriptomic and proteomic readouts that allows us to profile dual responses in tissue exposed to sEV “messages”—capturing both short-term transcriptomic shifts in the tissue and long-term changes in protein cargo of secreted EVs (the “reply”). Using spatial transcriptomics, we show that the short-term 1-day exposure to ovarian cancer-derived sEVs alters expression of 61 transcripts in secretory cells, the progenitor of HGSOC, notably upregulating immune-related mRNA, including CXCL family chemokines, VCAM1, and pro-inflammatory mediators (NFKB1, IL1B, IFNA7/17). Additionally, we observed the long-term 14-day exposure to sEVs alters the expression of 7 transcripts and 25 EV cargo proteins of fallopian tube derived EVs (“secondary release EVs”) following stimulus from cancer EVs. Together, tissue transcriptomics and tissue-derived EV proteomics indicate that ovarian cancer derived sEVs rewire target cell signaling to modify the tubal immune landscape. This study provides insights into the early molecular changes associated with the pathogenesis of ovarian cancer in its tissue of origin, providing a platform to study EV-tissue interactions and identify how sEVs drive cell signaling reprogramming in hFTE.
2025-07-15 | GSE300490 | GEO
Project description:Human fallopian tube epithelial organoids with TP53 mutation recapitulate features of serous tubal intraepithelial carcinoma (STIC) Judith Kraiczy, Bo Yu Gynecologic Oncology, Volume 203, 2025, Pages 198-208, ISSN 0090-8258, https://doi.org/10.1016/j.ygyno.2025.10.038. ABSTRACT Objective Serous tubal intraepithelial carcinoma (STIC) is the immediate precursor lesion for high-grade serous ovarian carcinoma (HGSOC) and harbors universal TP53 mutations. The lack of an appropriate in vitro model for STIC presents a major challenge in studying its pathogenesis. We aimed to develop a human in vitro model that mimics STIC lesions. Methods Using CRISPR-Cas9 gene editing, we generated human fallopian tube epithelial organoids with TP53 loss-of-function mutations (TP53-/- FTOs). We characterized TP53-/- FTOs on a cellular and molecular level using immunofluorescence confocal imaging, copy number variation (CNV) analysis, and RNA sequencing. Results TP53-/- FTOs recapitulated key features of STIC lesions. They exhibited increased proliferation and nuclear abnormalities, including nuclear enlargement and atypical mitotic figures. Copy number variation analysis revealed aneuploidy in some TP53-/- FTOs. Compared to unedited controls, TP53-/- FTOs demonstrated significant transcriptomic changes, including the downregulation of DNA repair genes and upregulation of epithelial-mesenchymal transition (EMT) pathways. Similar to STIC lesions, TP53-/- FTOs showed a marked reduction in ciliated cells and ciliogenesis-associated gene expression. Conclusions These findings suggest that p53 loss in FTOs promotes a proliferative and genomically unstable state that is conducive to carcinogenesis. The TP53-/- FTO model we have generated provides a valuable tool for studying early events in ovarian carcinogenesis and for developing new strategies for the early detection and prevention of ovarian cancer.
2025-11-21 | GSE310429 | GEO
Project description:Human fallopian tube epithelial organoids with TP53 mutation recapitulate features of serous tubal intraepithelial carcinoma (STIC), Judith Kraiczy, Bo Yu, Gynecologic Oncology, Volume 203,2025, Pages 198-208, ISSN 0090-8258, https://doi.org/10.1016/j.ygyno.2025.10.038. SUMMARY Objective Serous tubal intraepithelial carcinoma (STIC) is the immediate precursor lesion for high-grade serous ovarian carcinoma (HGSOC) and harbors universal TP53 mutations. The lack of an appropriate in vitro model for STIC presents a major challenge in studying its pathogenesis. We aimed to develop a human in vitro model that mimics STIC lesions. Methods Using CRISPR-Cas9 gene editing, we generated human fallopian tube epithelial organoids with TP53 loss-of-function mutations (TP53-/- FTOs). We characterized TP53-/- FTOs on a cellular and molecular level using immunofluorescence confocal imaging, copy number variation (CNV) analysis, and RNA sequencing. TP53-/- FTOs recapitulated key features of STIC lesions. They exhibited increased proliferation and nuclear abnormalities, including nuclear enlargement and atypical mitotic figures. Copy number variation analysis revealed aneuploidy in some TP53-/- FTOs. Compared to unedited controls, TP53-/- FTOs demonstrated significant transcriptomic changes, including the downregulation of DNA repair genes and upregulation of epithelial-mesenchymal transition (EMT) pathways. Similar to STIC lesions, TP53-/- FTOs showed a marked reduction in ciliated cells and ciliogenesis-associated gene expression. Conclusions These findings suggest that p53 loss in FTOs promotes a proliferative and genomically unstable state that is conducive to carcinogenesis. The TP53-/- FTO model we have generated provides a valuable tool for studying early events in ovarian carcinogenesis and for developing new strategies for the early detection and prevention of ovarian cancer.
2025-11-21 | GSE310067 | GEO
Project description:Objective To investigate the influence that oviductal extracellular vesicles from patients with endometriosis exert on early embryo development. Design In vitro experimental study Setting University-affiliated hospital. Patient(s) Women with and without endometriosis who underwent hysterectomy (n = 15 in total). Intervention(s) None. Main Outcome Measure(s) Oviductal extracellular vesicles from patients with endometriosis (oEV-EMT) or without endometriosis (oEV-ctrl) were isolated and co-cultured with two-cell murine embryos for 75 hours. Blastocyst rates were recorded. RNA sequencing was used to identified the differentially expressed genes in blastocysts cultured either with oEV-EMT or with oEV-ctrl. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to identify potential biological processes in embryos that oEV-EMT affect. The functions of oEV on early embryo development were determined by reactive oxygen species (ROS) levels, mitochondrial membrane potentials, total cell numbers and apoptotic cell proportions. Result(s) Extracellular vesicles were successfully isolated from human Fallopian tubal fluid and their characterizations were described. The blastocyst rates were significantly decreased in the oEV-EMT group. RNA sequencing revealed that oxidative phosphorylation was down-regulated in blastocysts cultured with oEV-EMT. Analysis of oxidative stress and apoptosis at the blastocysts stage showed that embryos cultured with oEV-EMT had increased ROS level, decreased mitochondrial membrane potentials, and increased apoptotic index. Total cell numbers were not influenced. Conclusion(s) Oviductal extracellular vesicles from patients with endometriosis exert a negative influence on early embryo development.
2023-06-02 | GSE225323 | GEO
Project description:Serous tubal intraepithelial carcinomas (STIC lesions) in the human fallopian tube epithelium (hFTE) are theorized to give rise to high grade serous ovarian cancers (HGSOC). Small extracellular vesicles (sEVs) are known to mediate key signaling in both normal and cancerous tissues, but few ex vivo systems exist for studying sEV impact on hFTE tissue. Here, we present a microfluidic tissue culture platform with combined spatial transcriptomic and proteomic readouts that allows us to profile dual responses in tissue exposed to sEV “messages”—capturing both short-term transcriptomic shifts in the tissue and long-term changes in protein cargo of secreted EVs (the “reply”). Using spatial transcriptomics, we show that the short-term 1-day exposure to ovarian cancer-derived sEVs alters expression of 61 transcripts in secretory cells, the progenitor of HGSOC, notably upregulating immune-related mRNA, including CXCL family chemokines, VCAM1, and pro-inflammatory mediators (NFKB1, IL1B, IFNA7/17). Additionally, we observed the long-term 14-day exposure to sEVs alters the expression of 7 transcripts and 25 EV cargo proteins of fallopian tube derived EVs (“secondary release EVs”) following stimulus from cancer EVs. Together, tissue transcriptomics and tissue-derived EV proteomics indicate that ovarian cancer derived sEVs rewire target cell signaling to modify the tubal immune landscape. This study provides insights into the early molecular changes associated with the pathogenesis of ovarian cancer in its tissue of origin, providing a platform to study EV-tissue interactions and identify how sEVs drive cell signaling reprogramming in hFTE.
2025-07-15 | PXD066017 | Pride
Project description:We analysed the extracellular matrix (ECM) landscape of fresh, healthy tissues from human fallopian tube (FT), fimbria (FB, the tissue of origin of serous tubal intraepithelial lesions) and ovarian tissue (OV). The aim was to identify differentially expressed matrix proteins between FB and FT or OV which may promote the neoplastic transformation of serous tubal intraepithelial lesions (STICs) into high-grade serous ovarian cancer, HGSOC, and metastasis from the FB to the OV.
2022-06-20 | PXD023912 | Pride
Project description:Hydrosalpinx is common cause of tubal factor infertility in women in which the fallopian tube becomes blocked, fills with fluid, and consequently is nonfunctional. Single cell RNA-seq analysis has provided an unparalleled approach to characterize tissue types and explore pathologies in unbiased manner. Here we use scRNA-seq to define and compare major and rare cell types of the human fallopian tube in the healthy and hydrosalpinx disease state.
2022-04-12 | GSE178101 | GEO