Bedrick Bronwyn S, Courtright Laura, Zhang Jiahui, Snow Morgan, Amendola Isabela Landsteiner Sampaio, Nylander Elisabeth, Cayton-Vaught Kamaria, Segars James, Singh Bhuchitra
Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Reproductive Sciences & Women's Health Research, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
F S Rev. 2024 Jan;5(1). doi: 10.1016/j.xfnr.2024.01.003. Epub 2024 Feb 2.
To assess the current literature evaluating the epigenetics of endometriosis in humans.
A systematic review was conducted in accordance with the PRISMA guidelines within PubMed, EBSCOhost, Cochrane Library, Embase, Scopus, and Web of Science Core Collection. A comprehensive search strategy was developed by a data informationist. Observational and interventional studies assessing epigenetics in humans published in English up to January 15th, 2023, were included. Two reviewers independently screened studies evaluating the role of epigenetics in endometriosis. The risk of bias was assessed using Cochrane RoB 2.0 tool and the Newcastle-Ottawa scale. Extracted data were analyzed descriptively.
We identified 18.639 studies, of which 57 were included, comprising 1.623 patients with endometriosis and 1.243 controls. Among the 57 studies included, 50 (88%) were case-control studies, and 7 (12%) were cross-sectional. Fifty-nine percent of the studies were Asian, 25% were from America, 14% were European, and 2% were from Africa. Acetylation and methylation were the two main key histone modifications that were centered in this review. Accordingly, we classified the studies as those focusing on genome-wide methylation and those on histone acetylation. Several studies identified an association between endometriosis and hypermethylated genes, including the PGR-B, SF-1, and RASSF1A. The genes HOXA10, COX-2, IL-12B, and GATA6 were found to be hypomethylated in endometriotic tissue by several studies. In regards to histone modification, multiple studies reported that the acetylation levels of histones H3 and H4 affect multiple genes associated with endometriosis. In addition, HDAC2 was found to be elevated in endometriosis patients in two studies.
Several studies reported a significant difference between specific genes' methylation levels in endometrial biopsies and normal tissue, which suggests that DNA methylation may play an important role in the modulation of the genotype in endometriotic tissue. Acetylation and methylation are the two key histone modifications leading to differential gene expression in endometriotic tissues. The alterations in gene expression reported by the 57 studies can have direct implications on cell cycle growth, cell cycle arrest, and apoptosis and, therefore, might play a key role in the pathogenesis of endometriosis. This review offers insight that histone modifications need further research to evaluate their role as potential biomarkers and treatment targets for endometriosis. Although several key similarities were reported, there were some disagreements among the results, which might be attributable to the heterogeneity between studies. Further research with a more robust standardization is needed to validate the epigenetic changes in endometriosis.
评估目前关于人类子宫内膜异位症表观遗传学的文献。
按照PRISMA指南在PubMed、EBSCOhost、Cochrane图书馆、Embase、Scopus和Web of Science核心合集中进行了系统综述。由数据信息专家制定了全面的检索策略。纳入截至2023年1月15日发表的以英文撰写的评估人类表观遗传学的观察性和干预性研究。两名评审员独立筛选评估表观遗传学在子宫内膜异位症中作用的研究。使用Cochrane RoB 2.0工具和纽卡斯尔-渥太华量表评估偏倚风险。对提取的数据进行描述性分析。
我们识别出18639项研究，其中57项被纳入，包括1623例子宫内膜异位症患者和1243例对照。在纳入的57项研究中，50项（88%）为病例对照研究，7项（12%）为横断面研究。59%的研究来自亚洲，25%来自美洲，14%来自欧洲，2%来自非洲。乙酰化和甲基化是本综述重点关注的两种主要组蛋白修饰。因此，我们将研究分为关注全基因组甲基化的研究和关注组蛋白乙酰化的研究。多项研究确定子宫内膜异位症与高甲基化基因之间存在关联，包括孕激素受体B（PGR-B）、类固醇生成因子1（SF-1）和RASSF1A。多项研究发现HOXA10、环氧化酶-2（COX-2）、白细胞介素12B（IL-12B）和GATA结合蛋白6（GATA6）基因在子宫内膜异位症组织中低甲基化。关于组蛋白修饰，多项研究报告组蛋白H3和H4的乙酰化水平影响多个与子宫内膜异位症相关的基因。此外，两项研究发现子宫内膜异位症患者中组蛋白去乙酰化酶2（HDAC2）升高。
多项研究报告子宫内膜活检组织与正常组织中特定基因的甲基化水平存在显著差异，这表明DNA甲基化可能在子宫内膜异位症组织基因型调控中起重要作用。乙酰化和甲基化是导致子宫内膜异位症组织中基因表达差异的两种关键组蛋白修饰。57项研究报告的基因表达改变可能对细胞周期生长、细胞周期停滞和细胞凋亡有直接影响，因此可能在子宫内膜异位症的发病机制中起关键作用。本综述提供了见解，即组蛋白修饰需要进一步研究以评估其作为子宫内膜异位症潜在生物标志物和治疗靶点的作用。尽管报告了一些关键的相似之处，但结果之间存在一些分歧，这可能归因于研究之间的异质性。需要进行更严格标准化的进一步研究来验证子宫内膜异位症中的表观遗传变化。
