Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube, 755-8505, Japan.
J Ovarian Res. 2019 Feb 6;12(1):14. doi: 10.1186/s13048-019-0489-1.
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.
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.
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.
与在位子宫内膜（EE）相比，卵巢子宫内膜异位症（OE）中各种甾体激素受体的表达状态发生改变。例如，在 OE 中，雌激素受体 1（ESR1）的表达下调，其编码 ERα，孕激素受体（PGR）的表达下调，而雌激素受体 2（ESR2）的表达上调，其编码 ERβ。这些变化的原因尚不清楚。基因的特定区域的 DNA 甲基化可导致组织特异性基因表达。这些区域被称为组织依赖性和差异甲基化区域（T-DMR）。我们之前报道过，正常组织中 T-DMR 的 DNA 甲基化调控了 ESR1 的组织特异性表达。在本研究中，我们研究了 T-DMR 的异常 DNA 甲基化是否与 OE 中 ESR1、ESR2 和 PGR 表达改变有关。
通过定量 RT-PCR 测量 ESR1、ESR2 和 PGR 的基因表达水平。与 EE 相比，OE 中 ESR1 和 PGR 的表达水平显著降低，而 ESR2 的表达水平显著升高。用 Infinium HumanMethylation450K BeadChip 和亚硫酸氢盐测序法检测 DNA 甲基化状态。与 EE 相比，OE 中 ESR1 的 T-DMR 处的 DNA 甲基化显著升高，但 ESR2 和 PGR 的 DNA 甲基化状态没有明显差异。
OE 中 T-DMR 的异常 DNA 甲基化与 ESR1 表达受损有关，而与 ESR2 和 PGR 表达改变无关。
