Menstrual flow as a non-invasive source of endometrial organoids
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB39169 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4312200.fastq.gz | Fastqsanger.gz | |||
| ERR4312210.fastq.gz | Fastqsanger.gz | |||
| ERR4312201.fastq.gz | Fastqsanger.gz | |||
| ERR4312211.fastq.gz | Fastqsanger.gz | |||
| ERR4312202.fastq.gz | Fastqsanger.gz |
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Project description:Organoid cultures derived from menstrual flow faithfully replicate secretory phase endometrial glands and provide a novel, non-invasive technique for the clinical assessment of endometrial function. Paired organoid cultures derived from scratch biopsies and ensuing menstrual flow share the same transcriptome signature, responses to early pregnancy hormones, and pathological changes in cases of early-pregnancy loss. The technique opens new avenues for investigating endometrial function in cases of subfertility and gynaecological disorders.
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Project description:Repair after damage is essential for tissue homeostasis. Post-menstrual repair of the uterine endometrium is a unique cyclical manifestation of rapid, scar-free, tissue repair taking ~3-5 days. Skin repair post-wounding is slower (~2 weeks) and, in the case of chronic wounds, takes months/years to restore integrity. Herein, the unique ‘rapid-repair’ endometrial environment is translated to the ‘slower-repair’ skin environment. Menstrual fluid (MF), the milieu of post-menstrual endometrial repair, facilitates healing of endometrial and keratinocyte ‘wounds’ in vitro, promoting cellular adhesion and migration, stimulates keratinocyte migration in an ex vivo human skin-reconstruct model and promotes re-epithelialization in an in vivo porcine wound model. Proteomic analysis of MF identified a large number of proteins; several proteins were selected for further investigation, with the endometrium demonstrated as the source of these factors. Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration, differing significantly from currently available wound-repair treatments, which mainly promote proliferation. Development of these and other menstrual fluid factors into a ‘migration-inducing’ treatment paradigm will provide novel therapies for tissue repair.
2018-07-30 | PXD007234 | Pride
Project description:Assessment of the endometrium often necessitates a biopsy, which currently involves an invasive, transcervical procedure. Here, we present an alternative technique based on deriving organoids from menstrual flow. We demonstrate that organoids can be derived from gland fragments recovered from menstrual flow. To confirm they faithfully reflect the in vivo state we compared organoids derived from paired scratch biopsies and ensuing menstrual flow from patients undergoing in vitro fertilisation (IVF). We demonstrate that the two sets of organoids share the same transcriptome signature, derivation efficiency and proliferation rate. Furthermore, they respond similarly to sex steroids and early-pregnancy hormones, with changes in morphology, receptor expression, and production of 'uterine milk' proteins that mimic those during the late-secretory phase and early pregnancy. This technique has wide-ranging impact for non-invasive investigation and personalised approaches to treatment of common gynaecological conditions, such as endometriosis, and reproductive disorders, including failed implantation after IVF and recurrent miscarriage.
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Project description:The endometrium undergoes profound progesterone-driven remodeling during the secretory phase of the menstrual cycle in a process called decidualization. In the absence of pregnancy, circulating progesterone levels fall and tissue-wide inflammation and influx of neutrophils precede tissue breakdown and menstrual shedding. These changes are accompanied by wide-scale transcriptomic changes that co-ordinate temporal changes throughout the secretory phase. Here, we sequenced whole endometrial biopsies to identify molecular biomarkers that mark specific stages of the secretory phase, including pre-menstrual tissues. 20 biopsies were timed to specific phases of the secretory cycle based on the donor’s reported LH, the physical morphology of tissues observed via IHC and serum progesterone levels.
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Project description:Progress and advancement in assisted reproductive technologies (ART) and its outcomes are limited by the importance of research of endometrial receptivity being overlooked. Due to endometrial biopsy being invasive and in vitro studies lacking reproducibility in vivo, urine is an appealing alternative biofluid source for biomarker research as it can be collected in large quantities non-invasively. The discovery of extracellular vesicles (EVs) in urine (uEVs), has also opened a new avenue in this biomarker research, with these EVs harbouring thousands of proteins that hold promise for biomarker development. In this study urine was collected from human female volunteers and samples representing the different phases of the menstrual cycle were subjected to EV isolation via differential centrifugation and size exclusion chromatography. The resulting uEVs were analysed via Nanoparticle tracking analysis (NTA) to examine the different concentration and size of particles and proteomic analysis performed using shotgun label-free mass spectrometry on the uEV samples and neat urine samples. Our results showed that uEVs were found in numbers depending on the menstrual cycle phase but uEV size was not statistically altered during different stages of the menstrual cycle. Proteomics showed 50% of proteins detected in the neat urine were also present in the uEV samples with 813 proteins were unique in the uEV samples. Proteomics analysis also showed that the menstrual cycle phase affect the uEVs proteomic profile, with some proteins shown to be significantly upregulated and downregulated during the window of implantation phase of the cycle compared to the other non-receptive periods. This data highlights that uEVs characteristics are altered depending on the menstrual cycle phase suggesting the potential of uEVs being used as biomarkers for improving fertility.In this dataset we have the neat urine results.
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Project description:Biomarker discovery in pre-menstrual endometrial biopsies
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Project description:Current endometrial receptivity tests require an invasive method of collecting of endometrial biopsies that can cause general discomfort and adverse events such as infections, pain, and bleeding. Therefore, minimally-invasive methodologies for receptivity evaluation are needed. Cervical cells could offer a great potential for endometrial receptivity testing because cervical cell collection by cytobrush is a standardized, quick, simple, well tolerated, minimally invasive and routinely used sampling technique in everyday gynaecological practice. To date, no studies have evaluated the suitability of cervical cells for endometrial receptivity testing based on transcriptional profiling throughout the menstrual cycle. In this study, paired samples of the endometrium and cervical cells were obtained from 20 women in different menstrual cycle time-points in natural cycles and women undergoing hormonal replacement cycles. The gene expression profiles of cervical cells showed no apparent clustering according to their collection time and menstrual cycle phase. Transcriptome analysis identified only four (KIF2C, CENPF, HLA-DRB5 and CUTALP) differentially expressed genes between the early- and mid-secretory samples, suggesting that the transcriptomes of cervical cells, in contrast to endometrial tissue, do not exhibit significant differences during the window of implantation opening. The largest differences in the transcriptome of cervical cells were noticed in late-secretory phase, before initiation of menstruation. The results of our study suggested that cervical cells’ transcriptome does not reflect the gene expression pattern of endometrial tissue during the WOI and these cells offer little or no potential for endometrial receptivity diagnostics.
2023-07-09 | GSE221127 | GEO
Project description:Successful embryo implantation into a receptive endometrium requires mutual endometrial-embryo communication. Recently, the function of extracellular vehicles (EVs) in cell-to-cell interaction in embryo-maternal interactions has been investigated. We explored isolated endometrial derived EVs, using RL95-2 cells as a model of a receptive endometrium, influenced by menstrual cycle hormones estrogen (E2; proliferative phase) progesterone (P4; secretory phase) and estrogen plus progesterone (E2P4; the receptive phase). EV sized particles were isolated by differential centrifugation and size exclusion chromatography. Nanoparticle tracking analysis was used to examine the different concentration and size of particles and EV proteomic analysis per-formed using shotgun label-free mass spectrometry. Our results showed that although endome-trial derived EVs were secreted in numbers independent of hormonal stimulation, EVs sizes were statistically modified by it. Proteomics analysis showed that hormone treatment changes affect the endometrial EVs proteome, with proteins enhanced within the EV E2P4 group shown to be in-volved in different processes such as embryo implantation, endometrial receptivity, and embryo development, supporting the concept of a communication system between the embryo and the maternal endometrium via EVs.
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Project description:Proper decidualization is vital in preparation for a potential embryo receptivity, placentation, menstrual health and subsequent endometrial regeneration. Given the importance of extracellular vesicles (EVs) in intercellular communication, and recently in embryo implantation and indicators of menstrual cycle and fertility, we investigated their role during decidualization. Overall, this study provides an insight into distinct variation in sEV composition depending upon the level of decidualization of endometrial stromal cells, with the signaling potential to coordinate endometrial health ranging from embryo implantation, facilitating placentation and subsequent endometrial regeneration.
2021-11-17 | PXD026342 | Pride
Project description:Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. Therefore, we used Infinium HumanMethylation 450K BeadChip arrays to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases. Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases from 24 patients with endometriosis
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