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Methylation of a Novel CpG Island of Intron I Is Associated With Steroidogenic Factor I Expression in Endometriotic Stromal Cells

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Abstract

Steroidogenic factor I (SF-I), 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-I expression in endometrial and endometriotic stromal cells. Design: We had previously identified a novel CpG island in SF-I, which is located in the downstream intron I 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 l-kbp region around the previously identified CpG island in endometriotic cells compared with endometrial cells (P <.001). A strong correlation between SF-I mRNA levels and percentage methylation of the intron I region of the SF-I gene was observed in endometriotic cells (Spearman correlation coefficient,.96; P <.001). Conclusions: Methylation of the intron I region of the SF-I gene is associated with its expression in endometriotic cells. This CpG island therefore plays an important role in regulating SF-I expression.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, First Hospital of Beijing University, Beijing, 100034, China

    Qing Xue MD, PhD, Yang Xu MD, Huixia Yang MD, Lei Zhang MD, Jing Shang MD & Cheng Zeng MD

  2. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Ping Yin MD, PhD & Serdar E. Bulun MD

Authors
  1. Qing Xue MD, PhD
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  2. Yang Xu MD
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  3. Huixia Yang MD
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  4. Lei Zhang MD
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  5. Jing Shang MD
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  6. Cheng Zeng MD
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  7. Ping Yin MD, PhD
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  8. Serdar E. Bulun MD
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Correspondence to Qing Xue MD, PhD.

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Xue, Q., Xu, Y., Yang, H. et al. Methylation of a Novel CpG Island of Intron I Is Associated With Steroidogenic Factor I Expression in Endometriotic Stromal Cells. Reprod. Sci. 21, 395–400 (2014). https://doi.org/10.1177/1933719113497283

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