Clinical trial NCT05412771: Evolutive and Functional Bases of Menstruation in Women - 2
Official title: Bases Évolutives Et Fonctionnelles De La Menstruation Chez Les Femmes - 2
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Menstruation
Keywords: endometrium
comparative genomics
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2022-06-09
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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
* Covered by social security

Exclusion Criteria:

* 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
* Have received hormonal treatment within the three months prior to collection
* Have participated in a clinical study within 3 months prior to collection
* Have a personal history of breast, ovarian, body or cervical cancer
* Have a diagnosis of endometriosis
* Have a diagnosis of adenomyosis
* Have a diagnosis of Lynch syndrome
* Undergoing hysteroscopy for a condition other than those listed in the inclusion criteria
* Women who have not given written consent
* Women who are breastfeeding
* Women with a body mass index (BMI) of less than 18.5 or more than 30

Primary outcomes:
measure: Transcriptomics
timeFrame: 18 months
measure: Open chromatin analysis
timeFrame: 18 months
Secondary outcomes:
measure: Non-coding transcriptomics
timeFrame: 18 months
measure: 3D cell culture - establishment
timeFrame: 18 months
measure: 3D cell culture - structural evaluation
timeFrame: 18 months
measure: 3D cell culture - cell types evaluation
timeFrame: 18 months
measure: 3D cell culture - gene expression
timeFrame: 18 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Pitié salpétrière
Study officials:
References: