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Background  In ovarian endometriomas (OE), the expression statuses of various steroid hormone receptors are altered compared with their expression statuses in eutopic endometrium (EE). For example, in OE, the expressions of estrogen receptor 1 ( ESR1 ) ,  which encodes ERα, and progesterone receptor ( PGR ) are downregulated, while the expression of  ESR2,  which encodes ERβ, is upregulated. The causes of these changes are unclear. DNA methylation of a specific region of a gene can result in tissue-specific gene expression. Such regions are called tissue-dependent and differentially methylated regions (T-DMRs). We previously reported that the tissue-specific expression of  ESR1  is regulated by DNA methylation of a T-DMR in normal tissues .  In the present study, we examined whether aberrant DNA methylation of the T-DMR is associated with the altered expressions of  ESR1, ESR2 and PGR  in OE.    Results  Gene expression levels of  ESR1, ESR2  and  PGR  were measured by quantitative RT-PCR. The expression levels of  ESR1  and  PGR  were significantly lower and the expression level of  ESR2  was significantly higher in OE than in EE. DNA methylation statuses were examined with an Infinium HumanMethylation450K BeadChip and sodium bisulfite sequencing. DNA methylation at the T-DMRs of  ESR1  were significantly higher in OE than in EE, but no significant differences were observed in the DNA methylation statuses of  ESR2  and  PGR .    Conclusions  Aberrant DNA methylation of the T-DMR was associated with the impaired expression of  ESR1 , but not the altered expressions of  ESR2  and  PGR , in OE.

Aberrant DNA methylation suppresses expression of estrogen receptor 1 (ESR1) in ovarian endometrioma