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Epigenetics and Uterine Fibroids

  • Ryo Maekawa
  • Norihiro Sugino
Chapter
Part of the Comprehensive Gynecology and Obstetrics book series (CGO)

Abstract

The pathogenesis of uterine fibroids, the most common benign tumor in women, remains unclear. Environmental factors such as obesity, hypertension, and early menarche place women at greater risk for uterine fibroids. Epigenetic processes such as DNA methylation, histone modification, and microRNA expression play key roles in regulating gene expression and have been shown to be affected by environmental and other factors. Thus, uterine fibroids may be associated with epigenetic abnormalities caused by unfavorable environmental factors.

Several reports have investigated the epigenetic profiles of uterine fibroid and normal myometrium. The profiles of DNA methylation in the myometrium with and without fibroids were quite similar while those in fibroids were distinct. In uterine fibroids, the biological relevance of the aberrantly methylated and expressed genes was cancer process. Some of these genes include IRS1, which is related to tumor transformation, and others such as GSTM5, KLF11, DLEC1, and KRT19, which have tumor-suppressive roles. Some microRNAs including miR-21, mir-200, and let-7 were found to be dysregulated in uterine fibroids and associated with the growth and the accumulation of extracellular matrix of uterine fibroids via aberrant expression of the target genes. Many estrogen receptor (ER) alpha-target genes, which were associated with apoptosis and collagen production, had aberrant DNA methylation in the promoter, which contributes to an abnormal response to estrogen. Moreover, some recent reports have demonstrated that several microRNAs which are dysregulated in uterine fibroids aberrantly mediate the actions of estrogen and progesterone.

Epigenetic abnormalities and their related transcriptional aberration have been associated with tumorigenic or tumor-suppressive roles, which may trigger the transformation of a single cell into a tumor stem cell that will eventually develop into a monoclonal uterine fibroid tumor. After menarche, the epigenetically dysregulated responses to estrogen and progesterone contribute to the growth of uterine fibroids.

Keywords

Uterine fibroids Epigenetics DNA methylation microRNA Estrogen receptor 

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Ryo Maekawa
    • 1
  • Norihiro Sugino
    • 1
  1. 1.Department of Obstetrics and GynecologyYamaguchi University School of MedicineUbe, YamaguchiJapan

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