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

TL;DR

This study explores how follicular fluid, especially its cytokine IL-8, influences the growth and spread of endometrial cells, offering new insights into endometriosis development.

Contribution

The study reveals that IL-8 in follicular fluid promotes endometriotic cell viability and migration through chemotaxis and EMT markers.

Findings

Follicular fluid at 50% dilution significantly increased endometriotic cell viability after 24 hours.

IL-8 in follicular fluid induced chemotactic cell migration, especially with the highest IL-8 concentration pool.

Follicular fluid treatment altered EMT markers, suggesting a hybrid epithelial-mesenchymal state in endometriotic cells.

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.

See also the graphical abstract(Fig. 1).

Figures