IL-8 and follicular fluid: insights into the mechanisms of endometriosis development

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Abstract

Endometriosis is a common gynaecological condition characterised by the growth of endometrial-like tissue both within the muscular layer of the uterus and outside of it, affecting 10-15 % of women of reproductive age. This study investigated the role of the surrounding environment, specifically the potential role of follicular fluid (FF) and particularly its cytokine IL-8, in the growth and invasiveness of endometrial epithelial cells. Using the epithelial-like endometriotic cell line 12Z, we analysed cell viability and migration after exposure to three different FF pools at various dilutions. Our results demonstrated that FF increased cell viability, with the most significant effects at a 50 % (v/v) dilution after 24 h. Moreover, FF treatment reduced cell migration, while FF as a chemoattractant induced increased chemotactic cell migration, especially with pool FF1 as a chemoattractant. This FF pool contained the highest IL-8 concentration. Like FF, IL-8 showed a strong chemotactic effect, significantly reduced by inhibiting IL-8 receptors CXCR1 and CXCR2, confirming IL-8’s role in chemotaxis. FF treatment induced the EMT marker N-cadherin and enhanced E-cadherin, indicating a hybrid cell EMT state. In conclusion, our study demonstrates that FF, particularly through IL-8 signalling, plays a crucial role in the pathogenesis of endometriosis by enhancing cell viability and influencing migration. These findings provide insights into how the local microenvironment contributes to disease progression.
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IL-8 and follicular fluid: insights into the mechanisms of endometriosis development DOI: https://doi.org/10.17179/excli2025-8885Keywords: endometriosis, IL-8, biological fluids, CXCR1, CXCR2, follicular fluidsAbstract Endometriosis is a common gynaecological condition characterised by the growth of endometrial-like tissue both within the muscular layer of the uterus and outside of it, affecting 10-15 % of women of reproductive age. This study investigated the role of the surrounding environment, specifically the potential role of follicular fluid (FF) and particularly its cytokine IL-8, in the growth and invasiveness of endometrial epithelial cells. Using the epithelial-like endometriotic cell line 12Z, we analysed cell viability and migration after exposure to three different FF pools at various dilutions. Our results demonstrated that FF increased cell viability, with the most significant effects at a 50 % (v/v) dilution after 24 h. Moreover, FF treatment reduced cell migration, while FF as a chemoattractant induced increased chemotactic cell migration, especially with pool FF1 as a chemoattractant. This FF pool contained the highest IL-8 concentration. Like FF, IL-8 showed a strong chemotactic effect, significantly reduced by inhibiting IL-8 receptors CXCR1 and CXCR2, confirming IL-8’s role in chemotaxis. FF treatment induced the EMT marker N-cadherin and enhanced E-cadherin, indicating a hybrid cell EMT state. In conclusion, our study demonstrates that FF, particularly through IL-8 signalling, plays a crucial role in the pathogenesis of endometriosis by enhancing cell viability and influencing migration. These findings provide insights into how the local microenvironment contributes to disease progression. Downloads Additional Files Published How to Cite Issue Section Categories License Copyright (c) 2025 Anne Teresa Heinrich, Ada Leoni Terres-Wurtz, Elisa Vacca, Katrin E. Tagscherer, Bartosz Linek, Susanne Gebhard, Annette Hasenburg, Walburgis Brenner, Roxana Schwab This work is licensed under a Creative Commons Attribution 4.0 International License. Authors who publish in this journal agree to the following terms: - The authors keep the copyright and grant the journal the right of first publication under the terms of the Creative Commons Attribution license, CC BY 4.0. This licencse permits unrestricted use, distribution and reproduction in any medium, provided that the original work is properly cited. - The use of general descriptive names, trade names, trademarks, and so forth in this publication, even if not specifically identified, does not imply that these names are not protected by the relevant laws and regulations. - Because the advice and information in this journal are believed to be true and accurate at the time of publication, neither the authors, the editors, nor the publisher accept any legal responsibility for any errors or omissions presented in the publication. The publisher makes no guarantee, express or implied, with respect to the material contained herein. - The authors can enter into additional contracts for the non-exclusive distribution of the journal's published version by citing the initial publication in this journal (e.g. publishing in an institutional repository or in a book).

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