Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis

Fertil Steril. 2011 Mar 15;95(4):1421-7. doi: 10.1016/j.fertnstert.2011.01.031. Epub 2011 Feb 12.

Abstract

Objective: To determine [1] expression levels of both DNA methyltransferases (DNMTs) and methyl-CpG-binding domain proteins (MBDs) in human endometrium throughout the menstrual cycle and in eutopic and ectopic endometrium of patients with endometriosis and [2] hormone responsiveness of DNMT and MBD expression in explant cultures of proliferative phase endometrium.

Design: In vitro study.

Setting: Academic medical center.

Patient(s): Premenopausal women with and without endometriosis.

Intervention(s): Explant cultures of proliferative phase endometrium were treated with vehicle, 17β-E(2), or a combination of E(2) and P (E(2) + P) for 24 hours.

Main outcome measure(s): Expression levels of DNMT1, DNMT2, and DNMT3B and MBD1, MBD2, and MeCP2 with use of real-time quantitative polymerase chain reaction.

Result(s): Expression levels of DNMT1 and MBD2 were significantly higher in secretory-phase endometrium compared with proliferative endometrium and menstrual endometrium. In explant cultures, treatment with E(2) + P resulted in significant up-regulation of DNMT1 and MBD2. Expression levels of several DNMTs and MBDs were significantly lower in endometriotic lesions compared with eutopic endometrium of women with endometriosis and disease-free controls.

Conclusion(s): These findings suggest a role for DNMTs and MBDs in the growth and differentiation of the human endometrium and support the notion that endometriosis may be an epigenetic disease.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / biosynthesis*
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Endometriosis / enzymology
  • Endometriosis / genetics
  • Endometriosis / metabolism*
  • Endometrium / enzymology
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Female
  • Humans
  • Protein Structure, Tertiary / genetics
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Up-Regulation / genetics

Substances

  • DNA-Binding Proteins
  • MBD1 protein, human
  • MBD2 protein, human
  • Transcription Factors
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human
  • TRDMT1 protein, human