Voros Charalampos, Athanasiou Diamantis, Mavrogianni Despoina, Varthaliti Antonia, Bananis Kyriakos, Athanasiou Antonia, Athanasiou Aikaterini, Papadimas Georgios, Gkirgkinoudis Athanasios, Papapanagiotou Ioannis, Migklis Kyriaki, Vaitsis Dimitrios, Koulakmanidis Aristotelis-Marios, Mazis Kourakos Dimitris, Ivanidou Sofia, Daskalaki Maria Anastasia, Theodora Marianna, Antsaklis Panagiotis, Loutradis Dimitrios, Daskalakis Georgios
1st Department of Obstetrics and Gynecology, 'Alexandra' General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece.
IVF Athens Reproduction Center V. Athanasiou, 15123 Maroussi, Greece.
Int J Mol Sci. 2025 Jun 3;26(11):5363. doi: 10.3390/ijms26115363.
Exosomal microRNAs (ex-miRs), encapsulated in extracellular vesicles (EVs), play a vital role in facilitating paracrine communication among granulosa cells (GCs), cumulus cells (CCs), and the oocyte inside follicular fluid (FF). These small non-coding RNAs are crucial for regulating folliculogenesis, oocyte maturation, and early embryonic development via modulating intracellular signaling networks. Dysregulation o has been associated with reproductive disorders such as polycystic ovarian syndrome (PCOS), diminished ovarian reserve (DOR), and inadequate ovarian response (POR), impacting oocyte quality and fertility outcomes. This narrative review consolidates molecular data from current human and animal studies regarding ex-miR expression patterns, functional targets, and pathway involvement within the context of assisted reproductive technologies (ARTs). A literature-based analysis was undertaken, focusing on signaling pathways, pathogenic processes, and clinical implications. Specifically, ex-miRs-such as miR-21, miR-34c, miR-143-3p, miR-155-5p, miR-339-5p, and miR-424-5p-were identified as regulators of critical pathways including phosphoinositide 3-kinase (PI3K)-AKT, ERK1/2, TGF-β/SMAD, and Rb-E2F1. These ex-miRs regulate apoptosis, glycolysis, mitochondrial function, and cell cycle expansion to influence oocyte competence. Pathological patterns in PCOS and POR are associated with altered ex-miR expression that disrupts metabolic and developmental signaling. Research utilizing animal models confirmed that modifications in EV-associated miRNA influence in vitro maturation (IVM) efficiency and blastocyst quality. Ex-miRs serve as intriguing non-invasive biomarkers and potential therapeutic targets for ARTs. Their mechanical involvement in oocyte and follicular physiology positions them for integration into forthcoming precision-based infertility therapies. For its implementation in reproductive medicine, EV profiling requires standardization and further functional validation in clinical environments.
外泌体微小RNA（ex-miRs）包裹在细胞外囊泡（EVs）中，在促进颗粒细胞（GCs）、卵丘细胞（CCs）和卵泡液（FF）中的卵母细胞之间的旁分泌通讯中发挥着至关重要的作用。这些小的非编码RNA通过调节细胞内信号网络，对调节卵泡发生、卵母细胞成熟和早期胚胎发育至关重要。失调与多囊卵巢综合征（PCOS）、卵巢储备功能减退（DOR）和卵巢反应不良（POR）等生殖障碍有关，影响卵母细胞质量和生育结局。这篇叙述性综述整合了当前人类和动物研究中关于辅助生殖技术（ARTs）背景下ex-miR表达模式、功能靶点和途径参与的分子数据。进行了基于文献的分析，重点关注信号通路、致病过程和临床意义。具体而言，ex-miRs，如miR-21、miR-34c、miR-143-3p、miR-155-5p、miR-339-5p和miR-424-5p，被确定为关键途径的调节因子，包括磷酸肌醇3-激酶（PI3K）-AKT、ERK1/2、TGF-β/SMAD和Rb-E2F1。这些ex-miRs调节细胞凋亡、糖酵解、线粒体功能和细胞周期扩展，以影响卵母细胞的能力。PCOS和POR的病理模式与ex-miR表达改变有关，这会破坏代谢和发育信号。利用动物模型的研究证实，EV相关miRNA的改变会影响体外成熟（IVM）效率和囊胚质量。Ex-miRs是ARTs中有趣的非侵入性生物标志物和潜在的治疗靶点。它们在卵母细胞和卵泡生理学中的机械参与使其有望整合到未来基于精准的不孕症治疗中。为了在生殖医学中实施，EV分析需要在临床环境中进行标准化和进一步的功能验证。
