子宫内膜异位症的表观遗传失调:病理生理学和治疗的意义。

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2023-11-09 DOI:10.1210/endrev/bnad020
Ryan M Marquardt, Dinh Nam Tran, Bruce A Lessey, Md Saidur Rahman, Jae-Wook Jeong
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引用次数: 0

摘要

子宫内膜异位症是一种常见的妇科疾病,与盆腔疼痛和不孕有关。尽管经过了一个多世纪的研究,子宫内膜异位症的病因仍未达成科学共识。由于缺乏明确性,导致预防、诊断和治疗选择不够理想。子宫内膜异位症的遗传因素的证据很有趣,但有限;然而,近年来,通过临床研究、体外细胞培养实验和体内动物模型,在确定表观遗传学在子宫内膜异位症发病机制中的作用方面取得了重大进展。主要发现包括子宫内膜异位症相关的DNA甲基转移酶和去甲基化酶、组蛋白去乙酰化酶、甲基转移酶和去甲基化酶以及染色质结构调节因子的差异表达。mirna在控制子宫内膜和子宫内膜异位症的表观遗传调节因子方面也有新的作用。这些表观遗传调节因子的变化导致不同的染色质组织和DNA甲基化,其结果是独立于基因序列的基因表达。与类固醇激素产生和信号、免疫调节、子宫内膜细胞身份和功能相关的基因的表观遗传表达改变都已被确定,并似乎在子宫内膜异位症和导致不孕的病理生理机制中发挥作用。这篇综述总结并批判性地讨论了早期的精液发现,最近越来越多的证据表明表观遗传学对子宫内膜异位症的病理生理有贡献,以及对拟议的表观遗传学靶向治疗的影响。
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Epigenetic Dysregulation in Endometriosis: Implications for Pathophysiology and Therapeutics.

Endometriosis is a prevalent gynecological condition associated with pelvic pain and infertility. Despite more than a century of research, the etiology of endometriosis still eludes scientific consensus. This lack of clarity has resulted in suboptimal prevention, diagnosis, and treatment options. Evidence of genetic contributors to endometriosis is interesting but limited; however, significant progress has been made in recent years in identifying an epigenetic role in the pathogenesis of endometriosis through clinical studies, in vitro cell culture experiments, and in vivo animal models. The predominant findings include endometriosis-related differential expression of DNA methyltransferases and demethylases, histone deacetylases, methyltransferases, and demethylases, and regulators of chromatin architecture. There is also an emerging role for miRNAs in controlling epigenetic regulators in the endometrium and endometriosis. Changes in these epigenetic regulators result in differential chromatin organization and DNA methylation, with consequences for gene expression independent of a genetic sequence. Epigenetically altered expression of genes related to steroid hormone production and signaling, immune regulation, and endometrial cell identity and function have all been identified and appear to play into the pathophysiological mechanisms of endometriosis and resulting infertility. This review summarizes and critically discusses early seminal findings, the ever-growing recent evidence of epigenetic contributions to the pathophysiology of endometriosis, and implications for proposed epigenetically targeted therapeutics.

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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
期刊最新文献
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