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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-A02779-32 | Registry Identifier | IDRCB |
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Menstruation corresponds to the shedding of the uterine lining when fecundation has not occurred. This is a recent evolutionary innovation in primates, and the cellular and genetic changes that led to the acquisition of menstruation are not well understood. Additionally, the uterine lining is poorly characterized in humans across the menstrual cycle, which hinders both evolutionary and medically-relevant analyses.
In this study, the research team are collecting uterine endometrial tissue samples from female donors undergoing uterine surgery for benign conditions, to profile gene expression and gene regulatory elements in the major cell types that compose the uterine lining during the secretive phase of the menstrual cycle. The investigators will compare this data to similar samples collected from other primates at the same time point in the female hormonal cycle.
The objective is to identify genes that have acquired novel regulation and/or expression patterns and which may be involved in menstruation, as well as better characterize the cellular and molecular pathways at work in the uterine lining of women for translational medicine purposes.
Collection:
The research team will collect endometrial biopsies or discarded tissue scraps from medical practice from 20 consenting female donors undergoing surgical hysteroscopy for benign uterine conditions.
Primary objective:
The research team will perform transcriptome sequencing and open chromatin profiling from the tissue samples and compare to similar data produced from non-human primates that either do or do not menstruate. They will identify and characterize genes and non-coding regulatory elements differentially used in menstruating species and involved in the evolution of menstruation.
Secondary objectives:
The research team will profile and characterize non-coding RNAs expressed in the human endometrium.
The research team will establish 3D cell cultures (organoids) from the tissue samples for further functional validations of the primary objective.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Main cohort | Experimental | This is a single-arm study. Samples are collected from consenting donors undergoing surgery for medical purposes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hysteroscopy | Procedure | Samples will be collected from consenting patients undergoing a surgical hysteroscopy for medical purposes |
|
| Measure | Description | Time Frame |
|---|---|---|
| Transcriptomics | Characterisation of genes involved in the evolutionary establishment of menstruation: transcriptome sequencing and identification of genes differentially expressed between menstruating and non-menstruating species in each cell type using DeSEQ analysis (FDR-corrected p-value < 0.05) | 18 months |
| Open chromatin analysis | Characterisation of non-coding regulatory elements specifically involved in the evolutionary establishment of menstruation: open chromatin sequencing (ATAC-seq) and identification of non-coding genomic regions differentially activated between menstruating and non-menstruating species in each cell type using DeSEQ analysis (FDR-corrected p-value < 0.05) | 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Non-coding transcriptomics | Characterisation of non-coding transcripts expressed in the endometrium in menstruating and non-menstruating species in each cell type by transcriptome sequencing, transcript assembly and annotation of expressed non-coding transcripts in each genome | 18 months |
| 3D cell culture - establishment |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pitié salpétrière | Paris | France |
Data generated from tissue samples from donors who gave expressed consent will be shared in the European Genome-Phenome Database (EGA).
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| ID | Term |
|---|---|
| D015907 | Hysteroscopy |
| ID | Term |
|---|---|
| D003944 | Diagnostic Techniques, Obstetrical and Gynecological |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D004724 | Endoscopy |
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Obtaining 3D cell cultures ("organoids") to validate the observations of the main objective: proliferation and expansion time-course assessed by bright-field microscopy |
| 18 months |
| 3D cell culture - structural evaluation | Topographical evaluation of the 3D cell cultures with H/E and PAS staining | 18 months |
| 3D cell culture - cell types evaluation | Profiling of characteristic cell markers in the 3D cell cultures via immunochemistry and immunofluorescence staining (MUC1, Cytokeratin7, EPCAM, Vimentin, CD13, ESR, PGR) | 18 months |
| 3D cell culture - gene expression | Gene expression profiling of the 3D cell cultures by PCR to compare to the transcriptomes from fresh tissues. | 18 months |
| D003949 | Diagnostic Techniques, Surgical |
| D019060 | Minimally Invasive Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D013513 | Obstetric Surgical Procedures |
| D013509 | Gynecologic Surgical Procedures |
| D013519 | Urogenital Surgical Procedures |