Endometriosis is a chronic gynaecological disease characterised by the growth of endometrium outside the uterus. It affects 10% of childbearing age women. There is no cure for endometriosis. Hormonal treatments should be the first line therapy. The benefit-risk ratio of symptomatic treatment with hormone therapy varies greatly from one woman to another. The pathophysiology of endometriosis and the mechanisms of action of these treatments are still poorly understood. This may be due to the lack of an optimal experimental model for studying the disease. The aim of this project is to develop a complex ex vivo endometrial model recapitulating the organisation and properties of the human endometrium using innovative tissue bioengineering methods. This model will make it possible to develop a pre-clinical approach that predicts individual response to different types of hormonal treatment in order to optimise therapeutic choices and provide a better understanding of the effects of these treatments.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
90
Eutopic and ectopic endometrium biopsies, additional blood and peritoneal fluid sampling
Questionnaire on menstrual health and history of hormone treatments for the research purpose
Hôpital Femme Mère Enfant / GHE
Bron, France
RECRUITINGHôpital de la Croix-Rousse / GHN
Lyon, France
RECRUITINGViability of all the cells forming the complex endometrial tissue generated ex vivo by tissue bioengineering.
The viability of all the cells forming the complex endometrial tissue generated ex vivo by tissue bioengineering will be assessed either by flow cytometry (labelling with propidium iodide or 7-AAD) or by immunofluorescence (with lipophilic carbocyanine dyes). The scientists involved in the project reserve the right to modify these labelling techniques and the markers mentioned, depending on the technical and logistical challenges encountered during the tissue bioengineering stages.
Time frame: through study completion, an average of 18 months
Change in protein expression
Comparing changes in protein expression in the model of complex endometrial tissue generated ex vivo by tissue bioengineering (eutopic endometrium) in each donor, between control and endometriosis groups and between eutopic and ectopic endometrium in endometriosis group.
Time frame: through study completion, an average of 18 months
Change in gene expression
Comparing changes in gene expression in the model of complex endometrial tissue generated ex vivo by tissue bioengineering (eutopic endometrium) in each donor, between control and endometriosis groups and between eutopic and ectopic endometrium in endometriosis group.
Time frame: through study completion, an average of 18 months
Change in inflammation
The concentration (expressed in pg/gl) of the following cytokines will be measured using Luminex technology (Bio-Plex 200 analyser): Interleukin (IL) 1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40/p70, IL-13, IL-15, IL-17, Tumor Necrosis Factor TNFα, interferons (IFN) IFN-α, IFN-γ, Granulocyte-Macrophage Colony Stimulating Factor GM-CSF, Macrophage Inflammatory Protein MIP-1α, MIP-1β, Interferon gamma-induced protein 10 IP-10, Eotaxin, RANTES, and Monocyte Chemoattractant Protein-1 MCP-1. Changes in these inflammation markers concentration in the model of complex endometrial tissue generated ex vivo by tissue bioengineering (eutopic endometrium) in each donor, between control and endometriosis groups and between eutopic and ectopic endometrium in endometriosis group will be assessed.
Time frame: through study completion, an average of 18 months
Change in histological tissue structure
Comparing changes in histological tissue structure (density of glands open to the lumen and glands located in the basal layer of the endometrium expressed in number of glands/cm3 of tissue, measured with an haematoxiline-eosin stainings and using Image J software) in the model of complex endometrial tissue generated ex vivo by tissue bioengineering (eutopic endometrium) in each donor, between control and endometriosis groups and between eutopic and ectopic endometrium in endometriosis group.
Time frame: through study completion, an average of 18 months
Change in histological tissue structure
Comparing changes in histological tissue structure (thickness of the endometrium expressed in micrometer) in the model of complex endometrial tissue generated ex vivo by tissue bioengineering (eutopic endometrium) in each donor, between control and endometriosis groups and between eutopic and ectopic endometrium in endometriosis group.
Time frame: through study completion, an average of 18 months
Change in tissue elasticity
Comparing changes in tissue elasticity by assessing the speed of shear waves in the model of complex endometrial tissue generated ex vivo by tissue bioengineering (eutopic endometrium) in each donor, between control and endometriosis groups and between eutopic and ectopic endometrium in endometriosis group.
Time frame: through study completion, an average of 18 months
Change in steroid hormone physiology
Measurement of steroid hormones concentration levels in blood and comparison between control and endometriosis groups. Steroid hormones assays will be carried out using ELISA® technologies. The following hormones will be measured: prolactin, Luteinizing Hormone (LH), estradiol (E2), estrone, progesterone and Sex hormone-binding globulin SHBG. The unit of measurement is pg/ml for all hormones.
Time frame: At baseline
Steroid hormones in peritoneal fluid
Measurement of steroid hormones concentration levels in peritoneal fluid and comparison between control and endometriosis groups. Steroid hormones assays will be carried out using ELISA® technologies. The following hormones will be measured: prolactin, Luteinizing Hormone (LH), estradiol (E2), estrone, progesterone and Sex hormone-binding globulin SHBG. The unit of measurement is pg/ml for all hormones.
Time frame: At baseline
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