DNA methylation in endometriosis (Review)

Abstract

Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis.

Pathogenesis of endometriosis: the genetic/epigenetic theory

“…These changes are increasingly viewed as a consequence of genetic or epigenetic polymorphism (154,(188)(189)(190). Other epigenetic changes (191)(192)(193)(194)(195)(196) comprise methylation, demethylation of DNA and modifications in histone code (193,197,198).…”

Pathogenesis of deep endometriosis

“…Epigenetic changes, during fetal life (179), have become a focus of interest during the past decade (180)(181)(182)(183)(184). They comprise methylation and demethylation of DNA (181,185,186), modifications in the histone code in endometriosis tissue in comparison with the endometrium, and experimental modifications of the histone code in cell lines and animal species. Many aberrations have been described, leading to speculation but without a comprehensive view at present.…”

Aberrant methylation of the IL‐12B promotor region contributes to the risk of developing ovarian endometriosis

“…DNA methylation in the promoter region can directly prevent transcription factor binding (Tate & Bird, ) and change the chromatin structure to restrict access of transcription factors to the promoter (Bird & Wolffe, ). Accumulated evidence has shown that aberrant DNA methylation is a feature of several important human diseases, including endometriosis (Guo, ; Koukoura, Sifakis, & Spandidos, ). Several genes associated with endometriosis are known to have variations in DNA methylation patterns, including progesterone receptor‐B (Wu, Strawn, & Basir, ), homeobox A10 (Wu, Halverson, & Basir, ), estrogen receptor‐β (Xue, Lin, & Yin, ), E‐cadherin (Li, An, & Guan, ), steroidogenic factor 1 (Xue, Xu, & Yang, ) and cyclooxygenase‐2 genes (Zidan, Rezk, & Alnemr, ).…”