{"paper_id":"41e0bea2-6e1a-46e3-8785-b29a23b8c944","body_text":"Abstract\nImpairment of decidualization of eutopic human endometrial stromal cells (hESCs) may cause an increase in cell survival of endometrial tissue in the peritoneal cavity constituting a precondition for endometriosis development. Decidualization is a physiological process involving progesterone action and cAMP signaling. We here evaluated the effect of 8-Br-cAMP, the adenylate cyclase activator forskolin and of the progestin progesterone and medroxyprogesterone acetate (MPA) alone and in combination on decidualization induction using prolactin ELISA, and on cell size, cell granularity, and cell survival via flow cytometry in hESCs of patients with and without endometriosis. While progestins alone did not induce functional decidualization in hESCs, 8-Br-cAMP and forskolin induced decidualization in hESCs from both cohorts, whereas the induction of FOXO1 transcription and prolactin secretion by forskolin was significantly lower than by 8-Br-cAMP. 8-Br-cAMP- and forskolin-induced prolactin secretion was significantly enhanced by MPA, but not by progesterone. Decidualization entailed a decrease in cell size and in cell granularity. In general, hESCs from women with mild (ASRM I/II) as well as severe (ASRM III/IV) endometriosis in trend displayed a higher granularity, whereas mainly hESCs from severe endometriosis showed a stronger resistance to the induction of cell death after decidualization induction. In both cohorts, the amount of the decidual marker protein prolactin rather exhibited an anti-proportional correlation to cell death induction during six day treatment. This study contributes to widen our understanding of the connection of decidualization and cell death in endometriosis.\nSimilar content being viewed by others\nData Availability\nThe data underlying this article will be shared on reasonable request to the corresponding author.\nCode Availability\nThis is not applicable.\nReferences\nGiudice LC. Endometriosis. N Engl J Med. 2010;362:2389–98. https://doi.org/10.1056/NEJMcp1000274.\nSimoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I, Brodszky V, Canis M, Colombo GL, DeLeire T, Falcone T, Graham B, Halis G, Horne A, Kanj O, Kjer JJ, Kristensen J, Lebovic D, Mueller M, et al. The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012;27:1292–9. https://doi.org/10.1093/humrep/des073.\nMeuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D'Hooghe T. 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Cancer Res. 2014;74:7060–8. https://doi.org/10.1158/0008-5472.Can-14-1784.\nAcknowledgments\nThe authors thank Hildegard Lax for support in statistical calculation.\nFunding\nThis work was supported by the Deutsche Forschungsgemeinschaft (DFG grant number GR 1138/14-1, BI 1963/6-1).\nAuthor information\nAuthors and Affiliations\nContributions\nAll authors participated in the design, interpretation of the studies and analysis of the data, and review of the manuscript. FP and JM conducted the experiments. APB and DBB supplied human endometrial samples. RG and APB created the concept. RG, APB, and BBS developed the methodology. FP and BBS validated the data. FP, JM, and RG wrote the manuscript. GW, BBS, and APB reviewed and edited the manuscript.\nCorresponding author\nEthics declarations\nEthical Approval\nThe study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Ethics Committee of the University of Düsseldorf (study number 5535, date of approval 24/05/2016).\nConsent to Participate\nThis is not applicable.\nConsent for Publication\nThis is not applicable.\nConflict 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\nPlatt, F., Moyer, J., Singer, B.B. et al. Forskolin versus cAMP-Induced Decidualization and Survival of Endometrial Stromal Cells of Endometriosis Patients. Reprod. Sci. 30, 2680–2691 (2023). https://doi.org/10.1007/s43032-023-01235-7\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-023-01235-7","source_license":"CC0","license_restricted":false}