Cited by 292Endometriosis Research and TreatmentAntioxidant Activity and Oxidative StressReproductive Biology and Fertility

Reactive Oxygen Species Controls Endometriosis Progression

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Ngô, Charlotte, Chéreau, Christiane, Nicco, Carole, Weill, Bernard, Chapron, Charles, Batteux, Frédéric·2009·The American Journal of Pathology

Abstract

Endometriosis is associated with chronic inflammation, and reactive oxygen species (ROS) are proinflammatory mediators that modulate cell proliferation. We have investigated whether the dysregulation of ROS production in endometriotic cells correlates with a pro-proliferative phenotype and can explain the spreading of this disease. Stromal and epithelial cells were purified from ovarian endometrioma and eutopic endometrium from 14 patients with endometriosis to produce four primary cell lines from each patient. ROS production, detoxification pathways, cell proliferation, and mitogen-activated protein kinase pathway activation were studied and compared with epithelial and stromal cell lines from 14 patients without endometriosis. Modulation of the proliferation of endometriosis by N-acetyl-cysteine, danazol, and mifepristone was tested in vitro and in 28 nude mice implanted with endometriotic tissue of human origin. Endometriotic cells displayed higher endogenous oxidative stress with an increase in ROS production, alterations in ROS detoxification pathways, and a drop in catalase levels, as observed for tumor cells. This increase in endogenous ROS correlated with increased cellular proliferation and activation of ERK1/2. These phenomena were abrogated by the antioxidant molecule N-acetyl-cysteine both in vitro and in a mouse model of endometriosis. Human endometriotic cells display activated pERK, enhanced ROS production, and proliferative capability. Our murine model shows that antioxidant molecules could be used as safe and efficient treatments for endometriosis.

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Crossref · 10.2353/ajpath.2009.080804

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  1. Vinatier D, Dufour P, Oosterlynck D: Immunological aspects of endo- metriosis. Hum Reprod Update 1996, 2:371-384
  2. Aebi H: Catalase in vitro. Methods Enzymol 1984, 105:121-126
  3. Murk W, Atabekoglu CS, Cakmak H, Heper A, Ensari A, Kayisli UA, Arici A: ERK activity in the human endometrium: possible roles in the pathogenesis of endometriosis. J Clin Endocrinol Metab 2008, 93:3532-3540

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Authors
Ngô, C., Chéreau, C., Nicco, C., Weill, B., Chapron, C., & Batteux, F.
Affiliations
Hôpital Cochin (FR)
Corresponding author
Batteux, Frédéric
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2009-07
Volume
175
Issue
1
Pages
225-234
ISSN
0002-9440 (ISSN-L)
OpenAlex
W2006808109
Cited by
292
References
39
Citations by year
2026: 12 · 2025: 18 · 2024: 15 · 2023: 24 · 2022: 20 · 2021: 23 · 2020: 18 · 2019: 13 · 2018: 16 · 2017: 15 · 2016: 14 · 2015: 18 · 2014: 17 · 2013: 20 · 2012: 21
FWCI
18.84
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords
endometriosis, reactive oxygen species, oxidative stress, endometrioma, endometrial stromal cells, endometrial epithelial cells, cell proliferation, ERK1/2 activation, MAPK signaling, catalase, N-acetylcysteine, antioxidants, danazol, mifepristone, chronic inflammation, xenograft mouse model
MeSH terms
Adult, Animals, Antioxidants, Catalase, Cell Line, Endometriosis, Female, Humans, Hydrogen Peroxide, Mice, Nude, Superoxide Dismutase, Blotting, Western, Reactive Oxygen Species, Oxidative Stress, Disease Progression, Extracellular Signal-Regulated MAP Kinases, Cell Proliferation, Mice

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