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 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. 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.

中文翻译：

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microRNA在卵巢功能中的作用以及在生育力保存方面向新型治疗策略的过渡：从实验台到未来的临床应用。

背景技术肿瘤学中的新治疗方法已经将癌症从确定的死刑转变为慢性疾病。但是，许多此类治疗的脱靶毒性仍然有待克服的挑战。肿瘤疗法可能导致女性未来的不孕。考虑到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药理学选择非常有吸引力。在这种情况下，转录组学和表观基因组学领域的进步已将称为microRNA（miRNA）的小型非编码RNA引起了肿瘤学的关注。MicroRNA在卵泡发育中也起着关键作用，它是卵泡生长的调节剂，闭锁和类固醇生成。它们也参与DNA损伤修复反应，它们本身可以在化学疗法中进行调节。由于这些原因，miRNA可能是在肿瘤治疗期间开发新的保护性疗法的有趣目标。这篇综述总结了miRNA在生殖中的生理作用。考虑到最近在肿瘤学中基于miRNA治疗的策略，我们强调了它们作为生育力保护目标的潜在兴趣，并提出了未来的策略，以实现从实验室到临床的过渡。目的和理由如何使用miRNA治疗方法来开发新的辅助保护性疗法，以减少由细胞毒性肿瘤治疗引起的卵巢损害？搜索方法到2019年，使用PubMed和Google Scholar数据库对英语文献进行了系统搜索，描述了miRNA在卵巢中的作用及其在肿瘤学中的诊断和靶向治疗的用途。个人数据说明了针对性腺和减少化疗引起的滤泡损伤的miRNA治疗策略。结果这篇综述概述了miRNA作为基因调节剂的重要性，并强调了肿瘤学的洞察力可以激发肿瘤育性领域新的佐剂策略这一事实。纳米技术的最新进展为使用下一代miRNA纳米载体进行药物开发提供了机会。对儿童的影响尽管这些疗法的免疫原性和毒性仍然存在一些障碍，并且关于将miRNA特异性地传递到卵巢中仍然存在改善的空间，但我们相信，将来，miRNA可以被开发为功能强大且非特异性的。保护生育力的侵入性工具。