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.
Be between 18 and 50 years old.
Have mensturation at the time of their participation
Have given their written consent
Have an indication for surgery of hysteroscopy for removal of a polyp and/or fibroid and/or endometrial, endometrialctomy for presumed benign pathology and/or management of a uterine malformation, scheduled between days 21 and 25 of their menstrual cycle
Using an intrauterine device contraceptive method during the study or within the previous three months
To be Pregnant at the time of collection
Have been pregnant in the three months prior to collection
Have had amenorrhoea in the three months prior to collection
Single group
Hysteroscopy
Procedure/SurgerySamples will be collected from consenting patients undergoing a surgical hysteroscopy for medical purposes
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)
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)
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
3D cell culture - establishment
Obtaining 3D cell cultures ("organoids") to validate the observations of the main objective: proliferation and expansion time-course assessed by bright-field microscopy
3D cell culture - structural evaluation
Topographical evaluation of the 3D cell cultures with H/E and PAS staining
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)
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