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Could DNA hydroxymethylation be crucial in influencing steroid hormone signaling in endometrial biology and endometriosis?
Molecular Reproduction and Development ( IF 2.7 ) Pub Date : 2019-11-20 , DOI: 10.1002/mrd.23299
Vishakha Mahajan 1 , Cynthia Farquhar 2 , Anna P Ponnampalam 1, 2, 3
Affiliation  

Endometriosis affects 10% of reproductive-aged women. It is characterized by the growth of the endometrium, outside the uterus and is associated with infertility and chronic abdominal pain. Lack of noninvasive diagnostic tools and early screening tests results in delayed treatment and subsequently increased disease severity. Endometriosis is a disease associated with a deregulated hormonal response, therefore, understanding the molecular mechanisms that govern this hormonal interplay is of paramount importance. DNA methylation is an epigenetic mark that regulates gene expression and is often associated with genes that code for steroid receptors and enzymes associated with estrogen synthesis and metabolism in endometriosis. DNA hydroxymethylation, which is structurally similar to methylation but functionally different, is a biologically critical mechanism that is also known to regulate gene expression. Ten Eleven Translocation (TET) proteins mediate hydroxymethylation. However, the role of DNA hydroxymethylation or TETs in the endometrium remains relatively unexplored. Currently, the "gold standard" technique used to study methylation patterns is bisulfite genomic sequencing. This technique also detects hydroxymethylation but fails to distinguish between the two, thereby limiting our understanding of these two processes. The presence of TETs in the male and female reproductive tract and its contribution to endometrial cancer makes it an important factor to study in endometriosis. This review summarizes the role of DNA methylation in aberrant steroid hormone signaling and hypothesizes that hydroxymethylation could be a factor influencing hormonal instability seen in endometriosis.

中文翻译:

DNA羟甲基化对于影响子宫内膜生物学和子宫内膜异位症中的类固醇激素信号传导是否至关重要?

子宫内膜异位症影响 10% 的育龄妇女。它的特点是子宫内膜在子宫外生长,并与不孕症和慢性腹痛有关。缺乏无创诊断工具和早期筛查测试会导致治疗延迟,进而导致疾病严重程度增加。子宫内膜异位症是一种与荷尔蒙反应失调相关的疾病,因此,了解控制这种荷尔蒙相互作用的分子机制至关重要。DNA甲基化是一种调节基因表达的表观遗传标记,通常与编码类固醇受体的基因以及与子宫内膜异位症中雌激素合成和代谢相关的酶有关。DNA羟甲基化,在结构上与甲基化相似但功能不同,是已知的调节基因表达的生物学关键机制。十一种十一易位 (TET) 蛋白介导羟甲基化。然而,DNA 羟甲基化或 TET 在子宫内膜中的作用仍然相对未探索。目前,用于研究甲基化模式的“黄金标准”技术是亚硫酸氢盐基因组测序。该技术也检测羟甲基化,但无法区分两者,从而限制了我们对这两个过程的理解。男性和女性生殖道中 TET 的存在及其对子宫内膜癌的影响使其成为研究子宫内膜异位症的重要因素。
更新日期:2019-11-01
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