Tesis doctorales: TESEO

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Ministerio de Universidades - Gobierno de España

Título: MOLECULAR ALTERATIONS IN EUTOPIC ENDOMETRIUM OF WOMEN WITH ENDOMETRIOSIS AND IMPLICATIONS IN ITS DIAGNOSTIC
Autor: Vallvé Juanico, Júlia
Universidad: Universidad Autónoma de Barcelona
Departamento: Biologia cel-lular fisiologia i d'immunologia
Fecha de Lectura: 25/10/2018
Mención Europeo / Mención Internacional: Concedido
Programa de doctorado: Programa de Doctorado en Biología Celular por la Universidad Autónoma de Barcelona
Dirección:
- Santamaria Costa, Xavier (DIRECTOR)
- GIL MORENO, ANTONIO (DIRECTOR)
- NAVARRO FERRETÉ, JOAQUIMA (TUTOR/PONENTE)
Tribunal:
- DIA FEIJOO, BERTA (PRESIDENTE)
- VILELLA MITJANA, FELIPE (SECRETARIO)
- Reis Soares, Sergio (VOCAL)
Descriptores:
- SECTOR DE LA SALUD
Localización: BIBLIOTECA DE COMUNICACIÓN Y HEMEROTECA GENERAL UAB

420873_1149696.pdf

Marcador: https://www.educacion.gob.es/teseo/mostrarRef.do?ref=1724544Añadir a favoritos.
Resumen:
Endometriosis is a benign disease that affects 10-15% of reproductive age women and the main symptoms are pain and infertility. Its diagnostic can be delayed for 6.7 years in average, and the final diagnostic is performed by laparoscopy. The main objective of this thesis was to find a new and less invasive tool than surgery to diagnose this disease. For this purpose, two objectives were performed; to find new biomarkers for the disease in eutopic endometrium and to study Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) as a putative biomarker for endometriosis. For the first objective, a discovery study of endometriosis biomarkers was done by RNA-High-Sequencing and a classifier was developed using Partial Least Squares (PLS) leave one out cross validation model. For this study, formalin-fixed paraffin embedded (FFPE) samples were used from all types of endometriosis and controls. It was not able to distinguish between types of disease but a high sensitivity and specificity to diagnose the disease in global was achieved. However, when we validated the model by increasing the sample size, only the 60% of patients could be diagnosed as endometriosis. In conclusion, this proposed model cannot be translated to the clinic. In the second objective, we studied LGR5 in eutopic endometrium by RNA-High-Sequencing and we discovered that these cells have a macrophage-like phenotype. We did not observe significant differences between healthy and diseased women and thus, LGR5 is not a good biomarker for the disease. However, we found that deep infiltrating endometriosis (DIE), the most aggressive type of the disease, overexpressed unique genes related to infertility. Hence, we concluded that LGR5 could be related to the aggressiveness of the disease as well as in reproductive outcomes. Since LGR5 positive cells displayed a macrophage-like phenotype, we studied macrophages in eutopic endometrium of diseased women and we found that they present a more pro-inflammatory phenotype than healthy endometrium, which could also influence to the pathophysiology of the disease and to the reproductive outcomes in these women.

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