OBJECTIVE To evaluate and compare the methylation pattern of Human Homeobox (HOX) clusters (A-D) and HOX cofactors in normal, eutopic, and ectopic endometrial tissues with ectopic and eutopic endometriosis organoids as advanced preclinical research models. DESIGN A chromatin immunoprecipitation (ChIP) array containing 84 genes was used to analyze methylation levels of HOX clusters (A-D) and HOX cofactors in normal, eutopic, and ectopic endometrial biopsy specimens as well as ectopic and eutopic endometriosis organoids. SETTING Reproductive biomedicine and cell science research centers. PATIENT(S) Nine healthy women without endometriosis (control) and 16 women diagnosed with endometriosis. INTERVENTION(S) Ectopic endometrial lesions were obtained using a laparoscopic procedure, and eutopic and control endometrium biopsy specimens were obtained using pipelle sampling. MAIN OUTCOME MEASURE(S) Methylation levels of HOX clusters (A-D) and HOX cofactors in eutopic and ectopic endometrial biopsy specimens, as well as eutopic and ectopic endometriosis organoids and normal endometrium. RESULT(S) Most HOX clusters (A-D) and HOX cofactors showed methylation alterations in ectopic/eutopic endometrial tissues and ectopic/eutopic endometriosis organoids compared with normal endometrium. These methylation alterations had the same pattern in ectopic/eutopic tissue biopsy specimens and ectopic/eutopic endometriosis organoids in most genes. A contrariwise methylation pattern was observed in 28 of 84 genes in the ectopic/eutopic tissue biopsy specimens and ectopic/eutopic endometriosis organoids. CONCLUSION(S) Because a conserved pattern of methylation alterations in endometriosis tissues and organoids was observed for most of the investigated genes (56 of 84), it can be concluded that endometriosis organoids maintain epigenetic changes. Therefore, our study suggests endometriosis organoids as a novel preclinical model to determine the epigenetic mechanisms that underlie endometriosis.

中文翻译：

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深入了解人类子宫内膜异位症类器官的表观遗传学：HOX 基因及其辅助因子的 DNA 甲基化分析

目的 评估和比较正常、在位和异位子宫内膜组织中人类同源盒 (HOX) 簇 (AD) 和 HOX 辅因子的甲基化模式，并将异位和在位子宫内膜异位类器官作为先进的临床前研究模型。设计 包含 84 个基因的染色质免疫沉淀 (ChIP) 阵列用于分析正常、在位和异位子宫内膜活检标本以及异位和在位子宫内膜异位症类器官中 HOX 簇 (AD) 和 HOX 辅因子的甲基化水平。设置生殖生物医学和细胞科学研究中心。患者 9 名没有子宫内膜异位症的健康女性（对照）和 16 名被诊断患有子宫内膜异位症的女性。干预（S）使用腹腔镜手术获得异位子宫内膜病变，使用吸管取样获得在位和对照子宫内膜活检标本。主要结果测量在位和异位子宫内膜活检标本以及在位和异位子宫内膜异位类器官和正常子宫内膜中 HOX 簇 (AD) 和 HOX 辅因子的甲基化水平。结果与正常子宫内膜相比，大多数 HOX 簇 (AD) 和 HOX 辅因子在异位/在位子宫内膜组织和异位/在位子宫内膜异位类器官中显示出甲基化改变。这些甲基化改变在异位/在位组织活检标本和异位/在位子宫内膜异位类器官的大多数基因中具有相同的模式。在异位/在位组织活检标本和异位/在位子宫内膜异位症类器官的 84 个基因中的 28 个中观察到相反的甲基化模式。结论(S) 因为对于大多数研究的基因（84 个中的 56 个）观察到子宫内膜异位症组织和类器官中甲基化改变的保守模式，可以得出结论，子宫内膜异位症类器官保持表观遗传变化。因此，我们的研究表明，子宫内膜异位症类器官是一种新的临床前模型，可以确定子宫内膜异位症的表观遗传机制。