Methylation of a novel CpG island of intron 1 is associated with steroidogenic factor 1 expression in endometriotic stromal cells

Reprod Sci. 2014 Mar;21(3):395-400. doi: 10.1177/1933719113497283. Epub 2013 Jul 30.

Abstract

Steroidogenic factor 1 (SF-1), a transcriptional factor essential for estrogen biosynthesis, is undetectable in endometrial stromal cells and aberrantly expressed in endometriotic stromal cells.

Objective: We tried to gain further insight into the mechanism for differential SF-1 expression in endometrial and endometriotic stromal cells.

Design: We had previously identified a novel CpG island in SF-1, which is located in the downstream intron 1 region. Here, we evaluated the methylation status of this CpG island.

Patients: We obtained the eutopic endometrium from disease-free participants (n = 8) and the walls of cystic endometriosis lesions of the ovaries from another group of participants (n = 8). None of the patients had received any preoperative hormonal therapy.

Interventions: Stromal cells were isolated from these 2 types of tissues and subjected to DNA bisulfite treatment and sequence analysis.

Results: The SF-1 messenger RNA (mRNA) levels in endometriotic stromal cells were significantly higher than those in endometrial stromal cells. Bisulfite sequencing showed strikingly increased methylation of a 1-kbp region around the previously identified CpG island in endometriotic cells compared with endometrial cells (P < .001). A strong correlation between SF-1 mRNA levels and percentage methylation of the intron 1 region of the SF-1 gene was observed in endometriotic cells (Spearman correlation coefficient, .96; P < .001).

Conclusions: Methylation of the intron 1 region of the SF-1 gene is associated with its expression in endometriotic cells. This CpG island therefore plays an important role in regulating SF-1 expression.

Keywords: CpG island; DNA methylation; SF-1; endometriosis; intron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • CpG Islands / physiology*
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Female
  • Gene Expression Regulation*
  • Humans
  • Introns / physiology*
  • Methylation
  • Steroidogenic Factor 1 / biosynthesis*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology

Substances

  • NR5A1 protein, human
  • Steroidogenic Factor 1