Abstract：
Adenomyosis is linked to dysmenorrhea and infertility. The pathogenesis of adenomyosis remains unclear, and little is known of the genetic and epigenetic changes in the eutopic endometrium in adenomyosis, which may predispose patients to the invasion and migration of endometrial tissues into the myometrium. Transcriptome studies have identified genes related to various cell behaviors but no targets for therapeutic intervention. The epigenetics of the eutopic endometrium in adenomyosis have rarely been investigated. Endometrial tissue was obtained from premenopausal women with (n = 32) or without adenomyosis (n = 17) who underwent hysterectomy aged 34-57 years at a tertiary hospital. The methylome and transcriptome were assessed by using a Methylation 450 K BeadChip array and Affymetrix expression microarray. Protein expression was examined by immunohistochemistry. Differential methylation analysis revealed 53 lowly methylated genes and 176 highly methylated genes with consistent gene expression in adenomyosis, including three genes encoding potassium ion channels. High expression of KCNK9 in the eutopic and ectopic endometria in patients with adenomyosis but not in normal controls was observed. Hormone-free, antibody-based KCNK9 targeting is a potential therapeutic strategy for adenomyosis-related dysmenorrhea, menorrhagia, and infertility.
摘要：
子宫腺肌病与痛经和不孕有关。子宫腺肌病的发病机制尚不清楚,对子宫腺肌病在位子宫内膜的遗传和表观遗传变化知之甚少，这可能使患者容易子宫内膜组织侵入和迁移到子宫肌层。转录组研究已经确定了与各种细胞行为相关的基因，但没有治疗干预的目标。子宫腺肌病在位子宫内膜的表观遗传学研究很少。子宫内膜组织取自在三级医院接受34-57岁子宫切除术的绝经前妇女（n=32）或无子宫腺肌病（n=17）。通过使用甲基化450KBeadChip阵列和Affymetrix表达微阵列评估甲基化组和转录组。通过免疫组织化学检查蛋白质表达。差异甲基化分析显示53个低甲基化基因和176个高甲基化基因在子宫腺肌病中具有一致的基因表达。包括三个编码钾离子通道的基因。在子宫腺肌病患者的在位和异位子宫内膜中观察到KCNK9的高表达，而在正常对照中未观察到。无激素,基于抗体的KCNK9靶向是子宫腺肌病相关痛经的潜在治疗策略，月经过多,和不孕症。
