OBJECTIVE To examine different expression profiles of plasma exosomal microRNA (miRNA) in polycystic ovary syndrome (PCOS) patients and controls, and their potential roles in PCOS pathogenesis. DESIGN Experimental study. SETTING Center for reproductive medicine. PATIENT(S) Seventy-five PCOS patients and 75 age-matched controls. INTERVENTION(S) Plasma exosomes miRNAs sequenced from 15 PCOS patients and 15 controls. MAIN OUTCOME MEASURE(S) Plasma exosomal miRNA expression and the correlation between PCOS phenotypes and miRNA expression. RESULT(S) The sequenced plasma exosomes miRNAs were further determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in a larger cohort, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Correlation analysis and receiver operating characteristic (ROC) curve analysis were used to determine the association between PCOS phenotypes and miRNA expression. The miRNA sequencing revealed 34 exosomal miRNAs were differentially expressed between PCOS patients and controls. Via qRT-PCR, five differentially expressed miRNAs (miR-126-3p, miR-146a-5p, miR-20b-5p, miR-106a-5p, and miR-18a-3p) were identified. The GO and KEGG analyses predicted their target functions included axon guidance, mitogen-activated protein kinase (MAPK) signaling, endocytosis, circadian rhythms, and cancer pathways. The expression of these miRNAs correlated with menstrual cycle, antral follicle count, hormone level, and combined yielded a ROC curve area of 0.781 in discriminating PCOS patients from the controls. CONCLUSION(S) Differential expression of plasma exosomal miRNAs may confer a risk of PCOS and may be helpful in distinguishing PCOS patients from controls. Certain miRNA expression may associated to the disease progression, which could help in an epigenetic understanding of the pathophysiology of PCOS.

中文翻译：

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多囊卵巢综合征女性血浆外泌体微RNA的差异表达谱

目的 检测多囊卵巢综合征 (PCOS) 患者和对照组血浆外泌体 microRNA (miRNA) 的不同表达谱，及其在 PCOS 发病机制中的潜在作用。设计 实验研究。设置生殖医学中心。患者 (S) 75 名 PCOS 患者和 75 名年龄匹配的对照。干预 (S) 从 15 名 PCOS 患者和 15 名对照中测序的血浆外泌体 miRNA。主要结果测量 (S) 血浆外泌体 miRNA 表达以及 PCOS 表型与 miRNA 表达之间的相关性。结果 (S) 测序的血浆外泌体 miRNA 在更大的队列中通过定量逆转录聚合酶链反应 (qRT-PCR) 进一步确定，然后是基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 分析。相关分析和受试者工作特征 (ROC) 曲线分析用于确定 PCOS 表型与 miRNA 表达之间的关联。miRNA 测序显示 34 种外泌体 miRNA 在 PCOS 患者和对照组之间差异表达。通过 qRT-PCR，鉴定了五种差异表达的 miRNA（miR-126-3p、miR-146a-5p、miR-20b-5p、miR-106a-5p 和 miR-18a-3p）。GO 和 KEGG 分析预测它们的目标功能包括轴突导向、丝裂原活化蛋白激酶 (MAPK) 信号传导、内吞作用、昼夜节律和癌症通路。这些 miRNA 的表达与月经周期、窦卵泡计数、激素水平相关，并结合产生了 0.781 的 ROC 曲线面积，可将 PCOS 患者与对照组区分开来。结论 (S) 血浆外泌体 miRNA 的差异表达可能会增加患 PCOS 的风险，并且可能有助于区分 PCOS 患者和对照组。某些 miRNA 表达可能与疾病进展有关，这可能有助于对 PCOS 病理生理学的表观遗传理解。