Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells.

Abstract

OBJECTIVE:

To define the expression and function of DNA methyltransferases (DNMTs) in response to decidualizing stimuli in endometriotic cells compared with healthy endometrial stroma.

DESIGN:

Basic science.

SETTING:

University research center.

PATIENT(S):

Premenopausal women with or without endometriosis.

INTERVENTION(S):

Primary cultures of stromal cells from healthy endometrium (E-IUM) or endometriomas (E-OSIS) were subjected to in vitro decidualization (IVD) using 1 μM medroxyprogesterone acetate, 35 nM 17β-estradiol, and 0.05 mM 8-Br-cAMP.

MAIN OUTCOME MEASURE(S):

Expression of DNMT1, DNMT3A, and DNMT3B in E-IUM and E-OSIS were assessed by quantitative real-time polymerase chain reaction and immunoblotting. Recruitment of DNMT3B to the promoters of steroidogenic factor 1 (SF-1) and estrogen receptor α (ESR1) was examined by chromatin immunoprecipitation.

RESULT(S):

IVD treatment reduced DNMT3B messenger RNA (74%) and protein levels (81%) only in E-IUM; DNMT1 and DNMT3A were unchanged in both cell types. Significantly more DNMT3B bound to the SF-1 promoter in E-IUM compared with E-OSIS, and IVD treatment reduced binding in E-IUM to levels similar to those in E-OSIS. Enrichment of DNMT3B across 3 ESR1 promoters was reduced in E-IUM after IVD, although the more-distal promoter showed increased DNMT3B enrichment in E-OSIS after IVD.

CONCLUSION(S):

The inability to downregulate DNMT3B expression in E-OSIS may contribute to an aberrant epigenetic fingerprint that misdirects gene expression in endometriosis and contributes to its altered response to steroid hormones.

• Authors: Matthew T Dyson, Toshiyuki Kakinuma, Mary Ellen Pavone, Diana Monsivais, Antonia Navarro, Saurabh S Malpani, Masanori Ono, Serdar E Bulun
• Journal: Fertility and sterility (Fertil Steril) Vol. 104 Issue 4 Pg. 953-963.e2 (Oct 2015) ISSN: 1556-5653 [Electronic] United States
• PMID: 26239024 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Chemical References

• DNA (Cytosine-5-)-Methyltransferases
• DNA methyltransferase 3B

Topics

• Adult
• Cells, Cultured
• DNA (Cytosine-5-)-Methyltransferases (genetics, metabolism)
• Embryo Implantation (genetics)
• Endometriosis (enzymology, genetics, pathology)
• Endometrium (enzymology, pathology)
• Female
• Gene Expression Regulation, Enzymologic
• Humans
• Middle Aged
• Ovarian Diseases (genetics, metabolism, pathology)
• Stromal Cells (enzymology, pathology)
• Tissue Distribution