{"paper_id":"f1d96ed2-18da-4449-b2ab-4e476a852bbd","body_text":"Abstract\nEndometriosis is a condition characterized by increased oxidative stress and chronic inflammation, which can be treated with progestins and other progesterone receptor ligands. However, some patients are refractory to this treatment and the reason is uncertain. Here we investigated the effects of the selective progesterone receptor modulator ulipristal acetate (UPA) on proliferation, reactive oxygen species (ROS), and proinflammatory cytokine production by endometriotic cells and endometrial cells from women with histologically proven endometriosis (n = 22) and endometriosis-free controls (n = 6). Epithelial and stromal cells were isolated and treated in triplicate for 24 h with 1 μM, 10 μM, or 100 μM UPA. Cells were tested for proliferation and ROS production, while cell supernatants were assayed for interleukin (IL)-6, C-C motif chemokine ligand 2 (CCL2), and tumor necrosis factor (TNF)-α concentrations. Proliferation, ROS production, and IL-6 and CCL2 secretion were increased in non-stimulated epithelial and stromal cells from endometriotic lesions compared to endometrial cells from endometriosis patients and controls. UPA induced a dose-dependent increase of cell proliferation only in endometriosis, while enhancing ROS production by all cell types evaluated. UPA reduced CCL2 production in controls but failed to do that in endometriosis, whereas TNF-α was undetectable. We conclude that treatment of endometriotic cells with UPA stimulated in vitro proliferation and ROS production and failed to revert the proinflammatory cytokine excess that characterized these cells, unravelling possible mechanisms of drug resistance in the treatment of endometriosis.\nSimilar content being viewed by others\nData Availability\nThe datasets generated during the current study are available from the corresponding author on request.\nCode Availability\nNot applicable.\nReferences\nTaylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397:839–52.\nChapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol. 2019;15:666–82.\nReis FM, Coutinho LM, Vannuccini S, Batteux F, Chapron C, Petraglia F. Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure. 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J Reprod Immunol. 2021;143:103248.\nAcknowledgements\nFMR received a grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil, # 201876/2017-5).\nAuthor information\nAuthors and Affiliations\nCorresponding authors\nEthics declarations\nEthics Approval\nThis study was conducted as an extension of the protocol titled “genomics and proteomics of endometriosis” approved by the local institutional review board (approval number 05-2006 provided by the “Comité de Protection des Personnes et des Biens dans la Recherche Biomédicale” of Paris Cochin).\nConsent to Participate\nAll participants gave written informed consent.\nConsent for Publication\nNot applicable.\nConflicts of Interest\nThe authors declare no competing interests.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nReis, F.M., Chouzenoux, S., Bourdon, M. et al. Effects of Ulipristal Acetate on Reactive Oxygen Species and Proinflammatory Cytokine Release by Epithelial and Stromal Cells from Human Endometrium and Endometriosis. Reprod. Sci. 31, 260–266 (2024). https://doi.org/10.1007/s43032-023-01341-6\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-023-01341-6","source_license":"CC0","license_restricted":false}