The role of microRNAs in ovarian function and the transition toward novel therapeutic strategies in fertility preservation: from bench to future clinical application
The role of microRNAs in ovarian function and the transition toward novel therapeutic strategies in fertility preservation: from bench to future clinical application
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DOI：
10.1093/humupd/dmz039
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发表时间：
2020-03-01
影响因子：
13.3
通讯作者：
Demeestere, I
中科院分区：
文献类型：
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作者：
Alexandri, C.;Daniel, A.;Demeestere, I
背景：肿瘤学的新治疗方法已经将癌症从某种死刑判决转变为一种慢性疾病。然而，关于许多这些治疗的脱靶毒性，仍然存在需要克服的挑战。肿瘤治疗可能导致女性未来不孕。鉴于这种对长期生活质量的负面影响，强烈建议保留生育能力。虽然配子和卵巢组织冷冻保存是常用的方法，但旨在减少肿瘤治疗期间卵巢损伤的新的基于药物的选择是非常有吸引力的。在这种情况下，转录组学和表观基因组学领域的进展使小的非编码rna，称为microRNAs (miRNAs)，成为肿瘤学的焦点。作为卵泡生长、闭锁和类固醇生成的调节因子，MicroRNAs在卵泡发育中也起着关键作用。它们也参与DNA损伤修复反应，它们自己也可以在化疗期间被调节。由于这些原因，mirna可能是在肿瘤治疗中开发新的保护性疗法的一个有趣的靶点。本文就mirna在生殖中的生理作用作一综述。考虑到肿瘤中基于miRNA治疗的最新发展策略，我们强调了它们作为生育能力保存目标的潜在兴趣，并提出了从实验室到临床过渡的未来策略。目的和原理：如何利用miRNA治疗方法开发新的辅助保护疗法，以减少细胞毒性肿瘤治疗引起的卵巢损伤？检索方法：使用PubMed和谷歌Scholar数据库对截至2019年的英文文献进行系统检索，描述mirna在卵巢中的作用及其在肿瘤诊断和靶向治疗中的应用。个人数据表明，miRNA治疗策略可以靶向性腺，减少化疗引起的卵泡损伤。结果：这篇综述概述了mirna作为基因调控因子的重要性，并强调了肿瘤学的见解可以激发肿瘤生育领域新的辅助策略。纳米技术的最新进步为使用下一代mirna -纳米载体开发药物提供了机会。更广泛的意义：尽管在这些治疗的免疫原性和毒性方面仍存在一些障碍，并且在将miRNAs特异性递送到卵巢方面仍有改进的空间，但我们相信，在未来，miRNAs可以发展成为强大的非侵入性生育保护工具。
BACKGROUND: New therapeutic approaches in oncology have converted cancer from a certain death sentence to a chronic disease. However, there are still challenges to be overcome regarding the off-target toxicity of many of these treatments. Oncological therapies can lead to future infertility in women. Given this negative impact on long-term quality of life, fertility preservation is highly recommended. While gamete and ovarian tissue cryopreservationare the usual methods offered, new pharmacological-based options aiming to reduce ovarian damage during oncological treatment are very attractive. In this vein, advances in the field of transcriptomics and epigenomics have brought small noncoding RNAs, called microRNAs (miRNAs), into the spotlight in oncology. MicroRNAs also play a key role in follicle development as regulators of follicular growth, atresia and steroidogenesis. They are also involved in DNA damage repair responses and they can themselves be modulated during chemotherapy. For these reasons, miRNAs may be an interesting target to develop new protective therapies during oncological treatment. This review summarizes the physiological role of miRNAs in reproduction. Considering recently developed strategies based on miRNA therapy in oncology, we highlight their potential interest as a target in fertility preservation and propose future strategies to make the transition from bench to clinic.OBJECTIVE AND RATIONALE: How can miRNA therapeutic approaches be used to develop new adjuvant protective therapies to reduce the ovarian damage caused by cytotoxic oncological treatments?SEARCH METHODS: A systematic search of English language literature using PubMed and Google Scholar databases was performed through to 2019 describing the role of miRNAs in the ovary and their use for diagnosis and targeted therapy in oncology. Personal data illustrate miRNA therapeutic strategies to target the gonads and reduce chemotherapy-induced follicular damage.OUTCOMES: This review outlines the importance of miRNAs as gene regulators and emphasizes the fact that insights in oncology can inspire new adjuvant strategies in the field of onco-fertility. Recent improvements in nanotechnology offer the opportunity for drug development using next-generation miRNA-nanocarriers.WIDER IMPLICATIONS: Although there are still some barriers regarding the immunogenicity and toxicity of these treatments and there is still room for improvement concerning the specific delivery of miRNAs into the ovaries, we believe that, in the future, miRNAs can be developed as powerful and non-invasive tools for fertility preservation.