Role of Epigenetic Modifications in The Aberrant Expression of The FOXP3 Gene in Endometriosis: A Case-Control Study

Various studies have reported aberrant function of the immune system in endometriosis. This highly prevalent disease can initiate and progress by numerous genetic and epigenetic alterations that affect immune system functions. Regulatory T cells (Treg) play an important role in controlling and prevention of endometriosis through regulating immune responses. Treg cells are regulated by the forkhead box P3 (FOXP3) gene. The aim of this study is to monitor any changes in gene expression and epigenetic profile of FOXP3) in endometriosis.

In the current case-control study, endometriotic tissues of women diagnosed with endometriosis (n=20) were compared with non-endometriotic women (n=20). Parallel to expression of this gene, chromatin immunoprecipitation (ChIP) coupled with real-time polymerase chain reaction (PCR) was used to quantify the incorporated levels of the epigenetic activating/repressing markers of H3K9ac/me2 into the FOXP3 promoter (n=6 in each group).

There was a significant reduction of FOXP3 in endometriotic tissues compared to the control group (P=0.001). Additionally, changes in the incorporated H3K9ac/me2 epigenetic markers were consistent with the expression results and supported the findings of this study.

Downregulation of FOXP3 expression may be involved in the pathogenesis of endometriosis beyond its critical role in Treg responses. In addition, histone modifications of H3K9ac/me2 in the FOXP3 promoter may regulate gene expression in endometriosis.