Ten-eleven translocation genes are downregulated in endometriosis

F. J. Roca, H. A. Loomans, A. T. Wittman, C. J. Creighton, Shannon Hawkins

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 HESFENDO. 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.

Original languageEnglish (US)
Pages (from-to)288-298
Number of pages11
JournalCurrent Molecular Medicine
Volume16
Issue number3
StatePublished - Mar 1 2016
Externally publishedYes

Keywords

  • 5-hydroxymethylcytosine (5-hmC)
  • Endometriosis
  • Epigenetic modifications
  • HESF (human endometrial stromal fibroblasts)
  • In vitro decidualization
  • TET (ten-eleven translocation) genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'Ten-eleven translocation genes are downregulated in endometriosis'. Together they form a unique fingerprint.

  • Cite this

    Roca, F. J., Loomans, H. A., Wittman, A. T., Creighton, C. J., & Hawkins, S. (2016). Ten-eleven translocation genes are downregulated in endometriosis. Current Molecular Medicine, 16(3), 288-298.