NRF2/GCL pathway in endometriosis
Abstract ID : 1685
Soumis par : Louis MARCELLIN Le 2016-03-14 21:43:05
Nom de la catégorie : SEUD CONGRESS
Typologie : Communication orale / Oral communication
Statut : validé
Autorisation de diffusion : Yes/Oui
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endogenous antioxidant effect that protect against oxidative damage triggered by inflammation, as a main part in the first
steps of the development of endometriosis lesion. Glutamate cysteine ligase (GCL), a target gene of NRF2, is the first
enzyme in the synthesis cascade of glutathione, an important endogenous antioxidant.
Materials /Patients and methods: We conduct a case-control laboratory study in a tertiary-care university from 2012 to
2014 to investigate whether the expression of NRF2 and GCL are deregulated in endometriotic tissues. Fitfty-one
patients were recruited for the study: 26 with histologically proven endometriosis and 25 unaffected women. A thorough
surgical examination of the abdominopelvic cavity was performed on all of the study participants. mRNA expressions of
NRF2 and GCL were investigated by quantitative RT-PCR in endometrium of disease-free women, and eutopic and
ectopic endometrium from endometriosis-affected women. Ex vivo stromal and epithelial cells were extracted from
endometrial and endometriotic biopsies from an another sets of patients to explore expression of NRF2 and GCL in this
both stromal and epithelial compartment. Expressions were further explored by immunohistochemistry in endometrium of
disease-free women and eutopic and ectopic endometrium of endometriosis-affected women. Peritoneal horn implants
from wild type black6 mice and from NRF2 -/- mice were compared and studied in histology.
Results: We found a mRNA levels of NRF2 and GCL significantly lower in ectopic endometrium of endometriosis-
affected women (p<0.001 and p<0.05, respectively). The western blot analysis of primary cultures cells revealed a
significant decreased o the expression of NRF2 and GCL in ectopic lesion in the epithelial cells (p<0.05) but not in the
stroma cells. The immunohistochemical analysis revealed a decreased staining in ectopic endometriotic tissues with
specific antibodies. The mean volume of ectopic horn implants was higher in case of NRF2 -/- (p<0.05) with a significant
increased staining for the red Sirius (p<0.05).
Conclusion: These findings indicate that expression of the transcription factor NRF2 and its effector GCL are both
heavily deregulated in endometriotic lesions.
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Mots clefs : endometriosis, NRF2, GCL, oxidative stress
Auteurs :
Références : , , ,
Auteurs
Louis Marcellin 1, Pietro Santulli 1, Sandrine Chouzenoux 2, Carole Nicco 2, Olivier CERCLES 2, Charles Chapron 1,
Frédéric Batteux 2,
1. Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) CochinService de Chirurgie
Gynécologie Obstétrique II et Médecine de la Reproduction, Université Paris Descartes, Sorbonne Paris Cité, Faculté de
Médecine, Paris, FRANCE
2. Equipe Stress Oxydant, Prolifération Cellulaire et Inflammation, Département Développement, Reproduction, Cancer,,
Inserm U1016, Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, FRANCE
Auteurs (raw format)
Marcellin Louis - email : louismarcellin@gmail.com Etablissement : Université Paris Descartes, Sorbonne Paris Cité,
Faculté de Médecine Service : Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU)
CochinService de Chirurgie Gynécologie Obstétrique II et Médecine de la Reproduction Ville : Paris Pays : FRANCE
Présentateur : Oui
Santulli Pietro - email : pietro.santulli@aphp.fr Etablissement : Université Paris Descartes, Sorbonne Paris Cité, Faculté
de Médecine Service : Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) CochinService
de Chirurgie Gynécologie Obstétrique II et Médecine de la Reproduction Ville : Paris Pays : FRANCE Présentateur : Non
Chouzenoux Sandrine - email : sandrine.chouzenoux@inserm.fe Etablissement : Inserm U1016, Université Paris
Descartes, Sorbonne Paris Cité, Faculté de Médecine Service : Equipe Stress Oxydant, Prolifération Cellulaire et
Inflammation, Département Développement, Reproduction, Cancer, Ville : Paris Pays : FRANCE Présentateur : Non
Nicco Carole - email : carole.nicco@inserm.fr Etablissement : Inserm U1016, Université Paris Descartes, Sorbonne
Paris Cité, Faculté de Médecine Service : Equipe Stress Oxydant, Prolifération Cellulaire et Inflammation, Département
Développement, Reproduction, Cancer, Ville : Paris Pays : FRANCE Présentateur : Non
CERCLES Olivier - email : olivier.cercles@inserm.fr Etablissement : Inserm U1016, Université Paris Descartes,
Sorbonne Paris Cité, Faculté de Médecine Service : Equipe Stress Oxydant, Prolifération Cellulaire et Inflammation,
Département Développement, Reproduction, Cancer, Ville : Paris Pays : FRANCE Présentateur : Non
Chapron Charles - email : charles.chapron@aphp.fr Etablissement : Université Paris Descartes, Sorbonne Paris Cité,