Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
Nuffield Department of Women's & Reproductive Health, Endometriosis CaRe Centre, University of Oxford, Oxford, UK.
Hum Reprod. 2023 Dec 4;38(12):2296-2311. doi: 10.1093/humrep/dead216.
Endometriosis is defined by the presence of extrauterine endometrial-like tissue, which can cause pain and infertility in 10% of reproductive-age women. To date, the pathogenesis is poorly understood resulting in significant diagnostic delays and poor therapeutic outcomes in many women. Small extracellular vesicles (sEVs) (<200 nm) are cell-derived vesicles containing molecules that can influence gene expression and behaviour in target cells. One such cargo are microRNAs (miRNAs), which are short, non-coding RNAs mostly 19-25 nucleotides in length that regulate post-transcriptional gene expression. This mini-review focuses on the role of sEV-miRNAs, which are conceivably better biomarkers for endometriosis than free miRNAs, which reflect the true pathophysiological state in the body, as sEV-encapsulated miRNAs are protected from degradation compared to free miRNA and provide direct cell-to-cell communication via sEV surface proteins. sEV-miRNAs have been implicated in the immunomodulation of macrophages, the proliferation, migration and invasion of endometrial cells, and angiogenesis, all hallmarks of endometriosis. The diagnostic potential of sEV-miRNA was investigated in one study that reported the sensitivity and specificity of two sEV-miRNAs (hsa-miR-22-3p and hsa-miR-320a-3p) in distinguishing endometriosis from non-endometriosis cases. Only three studies have explored the therapeutic potential of sEV-miRNAs in vivo in mice-two looked into the role of sEV-hsa-miR-214-3p in decreasing fibrosis, and one investigated sEV-hsa-miR-30c-5p in suppressing the invasive and migratory potential of endometriotic lesions. While early results are encouraging, studies need to further address the potential influence of factors such as the menstrual cycle as well as the location and extent of endometriotic lesions on miRNA expression in sEVs. Given these findings, and extrapolating from other conditions such as cancer, diabetes, and pre-eclampsia, sEV-miRNAs could present an attractive and urgently needed future diagnostic and therapeutic target for millions of women suffering from endometriosis. However, research in this area is hampered by lack of adherence to the International Society for Extracellular Vesicles 2018 guideline in separating and characterising sEVs, as well as the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project protocols.
子宫内膜异位症的定义是指存在子宫外类似子宫内膜的组织，这种组织可导致 10%的育龄期妇女出现疼痛和不孕。迄今为止，其发病机制尚不清楚，这导致许多女性的诊断延迟和治疗效果不佳。小细胞外囊泡（sEVs）（<200nm）是含有可影响靶细胞基因表达和行为的分子的细胞衍生囊泡。其中一种货物是 microRNAs（miRNAs），它们是长度为 19-25 个核苷酸的短非编码 RNA，可调节转录后基因表达。本篇综述主要关注 sEV-miRNAs 的作用，与反映体内真实病理生理状态的游离 miRNA 相比，sEV-miRNAs 可能是子宫内膜异位症更好的生物标志物，因为与游离 miRNA 相比，sEV 包裹的 miRNA 不易降解，并通过 sEV 表面蛋白提供直接的细胞间通讯。sEV-miRNAs 已被牵连到巨噬细胞的免疫调节、子宫内膜细胞的增殖、迁移和侵袭以及血管生成中，这些都是子宫内膜异位症的标志。有一项研究调查了 sEV-miRNA 的诊断潜力，该研究报告了两种 sEV-miRNA（hsa-miR-22-3p 和 hsa-miR-320a-3p）在区分子宫内膜异位症与非子宫内膜异位症病例中的敏感性和特异性。仅有三项研究在体内研究了 sEV-miRNA 的治疗潜力，两项研究探讨了 sEV-hsa-miR-214-3p 在减少纤维化中的作用，一项研究调查了 sEV-hsa-miR-30c-5p 抑制子宫内膜异位病灶侵袭和迁移潜能的作用。虽然早期结果令人鼓舞，但这些研究仍需进一步解决月经周期以及子宫内膜异位病灶的位置和范围等因素对 sEV 中 miRNA 表达的潜在影响。鉴于这些发现，并从癌症、糖尿病和子痫前期等其他疾病推断，sEV-miRNA 可能成为数以百万计患有子宫内膜异位症的女性有吸引力和迫切需要的未来诊断和治疗靶点。然而，由于缺乏对国际细胞外囊泡学会 2018 年指南中分离和表征 sEV 的遵循，以及世界子宫内膜异位症研究基金会子宫内膜异位症表型和生物样本库协调项目协议，该领域的研究受到阻碍。
