Research Laboratory in Human Reproduction, Faculty of Medicine, Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium.
Université de Tours, Faculty of Science and Technology, 37200 Tours, France.
Hum Reprod Update. 2020 Feb 28;26(2):174-196. doi: 10.1093/humupd/dmz039.
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 cryopreservation are 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.
How can miRNA therapeutic approaches be used to develop new adjuvant protective therapies to reduce the ovarian damage caused by cytotoxic oncological treatments?
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.
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.
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.
肿瘤学中的新治疗方法已经将癌症从死刑判决转变为慢性病。然而，许多这些治疗方法的非靶向毒性仍然是需要克服的挑战。肿瘤学治疗可能导致女性未来不孕。鉴于对长期生活质量的负面影响，强烈推荐生育力保存。虽然配子和卵巢组织冷冻保存是通常提供的方法，但旨在减少肿瘤治疗期间卵巢损伤的新型基于药理学的选择非常有吸引力。在这方面，转录组学和表观基因组学领域的进展使称为 microRNAs (miRNAs) 的小非编码 RNA 成为肿瘤学的焦点。miRNAs 作为卵泡生长、闭锁和类固醇生成的调节剂，在卵泡发育中也起着关键作用。它们还参与 DNA 损伤修复反应，并且在化疗期间可以自身被调节。由于这些原因，miRNAs 可能是开发肿瘤治疗期间新的保护治疗的一个有趣目标。本综述总结了 miRNAs 在生殖中的生理作用。鉴于肿瘤学中最近基于 miRNA 治疗的发展策略，我们强调了它们作为生育力保存靶点的潜在兴趣，并提出了将从基础研究到临床应用的未来策略。
miRNA 治疗方法如何用于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？
通过PubMed 和 Google Scholar 数据库对英文文献进行系统搜索，搜索时间截至 2019 年，描述了 miRNAs 在卵巢中的作用及其在肿瘤学中的诊断和靶向治疗中的应用。个人数据说明了 miRNA 治疗策略靶向性腺并减少化疗引起的卵泡损伤。
本综述概述了 miRNAs 作为基因调节剂的重要性，并强调了这样一个事实，即肿瘤学中的见解可以为性腺肿瘤学领域的新辅助策略提供灵感。纳米技术的最新进展为使用下一代 miRNA-纳米载体开发药物提供了机会。
尽管这些治疗方法的免疫原性和毒性仍然存在一些障碍，并且 miRNA 进入卵巢的特异性递送仍有改进的空间，但我们相信，在未来，miRNAs 可以开发为生育力保存的强大且非侵入性工具。
