{"paper_id":"7ff03cf4-3e66-4de1-8b49-7199e0192d09","body_text":"Abstract\nOur previous whole genome expression analysis of endometriomas suggested\ndysregulation of the ten-eleven translocation genes (TET1, TET2, and TET3), involved in converting 5-\nmethylcytosine to 5-hydroxymethylcytosine (5-hmC). The objective of this study was to validate the expression\nof TET genes in ectopic and eutopic endometrium and in primary cultures of human endometrial stromal\nfibroblasts (HESF) during in vitro decidualization and to quantify 5-hmC levels in patients with endometriosis.\nBlood, eutopic endometrium, and endometriotic tissues were collected at time of gynecologic surgery. HESF\ncultures were created from eutopic endometrium of women without (HESF-CONTROL) and with endometriosis\n(HESF-ENDO) and underwent in vitro decidualization. Genomic DNA from blood and tissues underwent\nquantification of the absolute amount of 5-hmC using ELISA. The expression of TET1, TET2, and TET3 was\ndecreased in endometriosis compared to non-endometriosis control eutopic endometrium. Surprisingly, the\nglobal amount of 5-hmC was higher in ectopic endometrium than control eutopic endometrium, while genomic\nDNA from blood of women with endometriosis contained statistically significantly less 5-hmC than women\nwithout endometriosis. Expression of TET1, TET2, and TET3 was decreased in non-decidualized HESFENDO.\nUpon in vitro decidualization, control HESF showed decreased expression of TET3, while decidualized\nHESF-ENDO showed no statistically significant change in expression of TET1, TET2, or TET3. These results\nindicate that the TET genes are downregulated in ectopic endometrium and in HESF-ENDO, and suggest for\nthe first time that TET genes play a role in endometriosis. High global amounts of 5-hmC in endometriotic\ntissues suggest unique epigenetic regulation in these tissues.\nKeywords: 5-hydroxymethylcytosine (5-hmC), endometriosis, epigenetic modifications, HESF (human endometrial stromal fibroblasts), in vitro decidualization, TET (ten-eleven translocation) genes.\n53\n16","source_license":"CC0","license_restricted":false}