期刊
CURRENT MOLECULAR MEDICINE
卷 16, 期 3, 页码 288-298出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1566524016666160225153844
关键词
5-hydroxymethylcytosine (5-hmC); endometriosis; epigenetic modifications; HESF (human endometrial stromal fibroblasts); in vitro decidualization; TET (ten-eleven translocation) genes
资金
- Baylor College of Medicine Department of Obstetrics and Gynecology
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/NIH, Specialized Cooperative Centers Program in Reproductive and Infertility Research [U54HD0077495]
- IDEA Award
- NCI [P30 CA125123]
- Genomic and RNA Profiling Core at Baylor College of Medicine
- NIH NCI grant [P30CA125123]
Our previous whole genome expression analysis of endometriomas suggested dysregulation of the ten-eleven translocation genes (TET1, TET2, and TET3), involved in converting 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). The objective of this study was to validate the expression of TET genes in ectopic and eutopic endometrium and in primary cultures of human endometrial stromal fibroblasts (HESF) during in vitro decidualization and to quantify 5-hmC levels in patients with endometriosis. Blood, eutopic endometrium, and endometriotic tissues were collected at time of gynecologic surgery. HESF cultures were created from eutopic endometrium of women without (HESF-CONTROL) and with endometriosis (HESF-ENDO) and underwent in vitro decidualization. Genomic DNA from blood and tissues underwent quantification of the absolute amount of 5-hmC using ELISA. The expression of TET1, TET2, and TET3 was decreased in endometriosis compared to non-endometriosis control eutopic endometrium. Surprisingly, the global amount of 5-hmC was higher in ectopic endometrium than control eutopic endometrium, while genomic DNA from blood of women with endometriosis contained statistically significantly less 5-hmC than women without endometriosis. Expression of TET1, TET2, and TET3 was decreased in non-decidualized HESF-ENDO. Upon in vitro decidualization, control HESF showed decreased expression of TET3, while decidualized HESF-ENDO showed no statistically significant change in expression of TET1, TET2, or TET3. These results indicate that the TET genes are downregulated in ectopic endometrium and in HESF-ENDO, and suggest for the first time that TET genes play a role in endometriosis. High global amounts of 5-hmC in endometriotic tissues suggest unique epigenetic regulation in these tissues.
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