The role of DNA hydroxymethylation and TET enzymes in placental development and pregnancy outcome.

IF 5.7 2区 医学 Q1 Medicine Clinical Epigenetics Pub Date : 2023-04-25 DOI:10.1186/s13148-023-01483-z
Sara Vasconcelos, Carla Caniçais, Susana M Chuva de Sousa Lopes, C Joana Marques, Sofia Dória
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Abstract

The placenta is a temporary organ that is essential for supporting mammalian embryo and fetal development. Understanding the molecular mechanisms underlying trophoblast differentiation and placental function may contribute to improving the diagnosis and treatment of obstetric complications. Epigenetics plays a significant role in the regulation of gene expression, particularly at imprinted genes, which are fundamental in the control of placental development. The Ten-Eleven-Translocation enzymes are part of the epigenetic machinery, converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). DNA hydroxymethylation is thought to act as an intermediate in the DNA demethylation mechanism and potentially be a stable and functionally relevant epigenetic mark on its own. The role of DNA hydroxymethylation during differentiation and development of the placenta is not fully understood but increasing knowledge in this field will help to evaluate its potential role in pregnancy complications. This review focuses on DNA hydroxymethylation and its epigenetic regulators in human and mouse placental development and function. Additionally, we address 5hmC in the context of genomic imprinting mechanism and in pregnancy complications, such as intrauterine growth restriction, preeclampsia and pregnancy loss. The cumulative findings show that DNA hydroxymethylation might be important for the control of gene expression in the placenta and suggest a dynamic role in the differentiation of trophoblast cell types during gestation.

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DNA羟甲基化和TET酶在胎盘发育和妊娠结局中的作用。
胎盘是支持哺乳动物胚胎和胎儿发育所必需的临时器官。了解滋养细胞分化和胎盘功能的分子机制可能有助于改善产科并发症的诊断和治疗。表观遗传学在基因表达的调控中起着重要的作用,特别是在印迹基因,这是控制胎盘发育的基础。10 - 11易位酶是表观遗传机制的一部分,将5-甲基胞嘧啶(5mC)转化为5-羟甲基胞嘧啶(5hmC)。DNA羟甲基化被认为是DNA去甲基化机制的一个中间环节,可能是一个稳定的、功能相关的表观遗传标记。DNA羟甲基化在胎盘分化和发育中的作用尚不完全清楚,但这一领域的知识的增加将有助于评估其在妊娠并发症中的潜在作用。本文综述了DNA羟甲基化及其表观遗传调控因子在人和小鼠胎盘发育和功能中的作用。此外,我们在基因组印迹机制和妊娠并发症(如宫内生长受限、先兆子痫和妊娠丢失)的背景下研究了5hmC。这些累积的研究结果表明,DNA羟甲基化可能对胎盘基因表达的控制很重要,并提示在妊娠期间滋养细胞类型的分化中起动态作用。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
期刊最新文献
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