H3K27me3-mediated epigenetic regulation of TET1 in the eutopic endometrium of women with endometriosis and infertility

Endometriosis is a common gynecological condition associated with chronic inflammation, epigenetic dysregulation, and infertility. The TET1 gene, involved in DNA demethylation, may be regulated by repressive histone modifications such as H3K27me3, but its role in endometriosis remains poorly understood. This study aimed to assess H3K27me3 enrichment in the promoter region of TET1 in eutopic endometrium of infertile and fertile women with endometriosis compared to fertile controls. Endometrial biopsies were collected during laparoscopy from 25 women (18 with endometriosis, 7 controls). Chromatin immunoprecipitation (ChIP) was performed to quantify H3K27me3 levels in three promoter regions of TET1. Analyses included stratification based on ChIP efficiency and subgroup comparisons according to fertility status and menstrual cycle phase. In overall comparisons, no significant differences in H3K27me3 levels were observed between endometriosis and control groups. However, after stratification by ChIP efficiency, region 2 showed a significant difference, indicating higher H3K27me3 enrichment in endometriosis samples (p = 0.04), confirmed after correction for multiple comparisons. Analyses by fertility status and cycle phase did not reveal additional significant differences. These findings suggest potential region-specific epigenetic alterations of TET1 in endometriosis. Due to the modest sample size and inconsistent subgroup effects, results should be interpreted with caution. Larger, cell-type-specific studies are warranted to clarify the relevance of H3K27me3-mediated TET1 regulation in endometriosis-related infertility.