外泌体微RNA在多囊卵巢综合征中的作用机制

doi:10.12280/gjfckx.20250624

摘要/Abstract

摘要：

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是一种以高雄激素血症、胰岛素抵抗、排卵障碍和卵巢多囊样改变为特征的常见生殖内分泌疾病。外泌体作为细胞间通讯的关键媒介，其携带的微RNA（microRNA，miRNA）在PCOS的发病机制中发挥重要作用。外泌体miRNA通过参与颗粒细胞糖酵解过程，改善能量代谢障碍，影响颗粒细胞增殖和卵泡发育，并且通过影响巨噬细胞极化改善卵巢局部炎症反应。同时，外泌体miRNA的表达异常与高雄激素血症、脂肪细胞分化和胰岛素抵抗密切相关。这些发现揭示了外泌体miRNA通过调控颗粒细胞功能、炎症反应、高雄激素血症以及代谢过程参与PCOS的发生发展，为其诊断和治疗提供了新的靶点。

关键词: 外泌体, 微RNAs, 多囊卵巢综合征, 粒层细胞, 炎症, 雄激素增多症, 代谢

Abstract:

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease characterized by hyperandrogenemia, insulin resistance, ovulation disorders, and polycystic changes in the ovaries. Exosomes, as key mediators of intercellular communication, carry microRNAs (miRNAs) that play a crucial role in the pathogenesis of PCOS.Exosomal miRNAs participate in the glycolysis process of granulosa cells, improve energy metabolism disorders, affect the proliferation of granulosa cells and follicular development, and improve the local ovarian inflammation response by influencing macrophage polarization. Meanwhile, the abnormal expression of exosomal miRNAs is closely related to hyperandrogenemia, adipocyte differentiation, and insulin resistance. These findings reveal that exosomal miRNAs are involved in the occurrence and development of PCOS by regulating granulosa cell function, inflammatory response, hyperandrogenemia, and metabolic processes, providing new targets for its diagnosis and treatment.

Key words: Exosomes, MicroRNAs, Polycystic ovary syndrome, Granulosa cells, Inflammation, Hyperandrogenism, Metabolism

丁宁, 韩延华, 王浩田, 孙畅, 匡洪影. 外泌体微RNA在多囊卵巢综合征中的作用机制[J]. 国际妇产科学杂志, 2026, 53(1): 73-77.

DING Ning, HAN Yan-hua, WANG Hao-tian, SUN Chang, KUANG Hong-ying. The Mechanism of Exosomal MicroRNAs in Polycystic Ovary Syndrome[J]. Journal of International Obstetrics and Gynecology, 2026, 53(1): 73-77.

参考文献 31

[1]	孔北华, 马丁, 段涛. 妇产科学[M]. 10版. 北京: 人民卫生出版社, 2024:384.
[2]	Dutta S, Sengupta P, Rao S, et al. Targeting Polycystic Ovary Syndrome (PCOS) Pathophysiology with Flavonoids: From Adipokine-Cytokine Crosstalk to Insulin Resistance and Reproductive Dysfunctions[J]. Pharmaceuticals(Basel), 2025, 18(10):1575. doi: 10.3390/ph18101575.
[3]	van Baal L, Tan S. Polycystic ovary syndrome as a gender-specific cardiometabolic risk factor[J]. Inn Med(Heidelb), 2023, 64(7):642-648. doi: 10.1007/s00108-023-01529-7.
[4]	Kulkarni S, Gupta K, Ratre P, et al. Polycystic ovary syndrome: Current scenario and future insights[J]. Drug Discov Today, 2023, 28(12):103821. doi: 10.1016/j.drudis.2023.103821.
[5]	Helvaci N, Yildiz BO. Polycystic ovary syndrome as a metabolic disease[J]. Nat Rev Endocrinol, 2025, 21(4):230-244. doi: 10.1038/s41574-024-01057-w. pmid: 39609634
[6]	Abdulmonem WA, Ahsan M, Mallick AK, et al. The Role of Exosomal miRNAs in Female Infertility: Therapeutic Potential and Mechanisms of Action[J]. Stem Cell Rev Rep, 2025, 21(5):1141-1159. doi: 10.1007/s12015-025-10869-w.
[7]	Zhang Z, Shi C, Wang Z. The physiological functions and therapeutic potential of exosomes during the development and treatment of polycystic ovary syndrome[J]. Front Physiol, 2023, 14:1279469. doi: 10.3389/fphys.2023.1279469.
[8]	Kumar MA, Baba SK, Sadida HQ, et al. Extracellular vesicles as tools and targets in therapy for diseases[J]. Signal Transduct Target Ther, 2024, 9(1):27. doi: 10.1038/s41392-024-01735-1.
[9]	Salehi R, Asare-Werehene M, Wyse BA, et al. Granulosa cell-derived miR-379-5p regulates macrophage polarization in polycystic ovarian syndrome[J]. Front Immunol, 2023, 14:1104550. doi: 10.3389/fimmu.2023.1104550.
[10]	Guo XR, Ma Y, Ma ZM, et al. Exosomes: The role in mammalian reproductive regulation and pregnancy-related diseases[J]. Front Physiol, 2023, 14:1056905. doi: 10.3389/fphys.2023.1056905.
[11]	Cui X, Lei X, Huang T, et al. Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA[J]. J Ovarian Res, 2024, 17(1):223. doi: 10.1186/s13048-024-01542-w. pmid: 39538292
[12]	Cao J, Huo P, Cui K, et al. Follicular fluid-derived exosomal miR-143-3p/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome[J]. Cell Commun Signal, 2022, 20(1):61. doi: 10.1186/s12964-022-00876-6. pmid: 35534864
[13]	Jiang X, Zhang Z, Hou M, et al. Plasma exosomes and contained MiRNAs affect the reproductive phenotype in polycystic ovary syndrome[J]. FASEB J, 2023, 37(7):e22960. doi: 10.1096/fj.202201940RR.
[14]	Wang M, Sun Y, Yuan D, et al. Follicular fluid derived exosomal miR-4449 regulates cell proliferation and oxidative stress by targeting KEAP1 in human granulosa cell lines KGN and COV434[J]. Exp Cell Res, 2023, 430(2):113735. doi: 10.1016/j.yexcr.2023.113735.
[15]	Salehi R, Wyse BA, Asare-Werehene M, et al. Androgen-induced exosomal miR-379-5p release determines granulosa cell fate: cellular mechanism involved in polycystic ovaries[J]. J Ovarian Res, 2023, 16(1):74. doi: 10.1186/s13048-023-01141-1. pmid: 37046285
[16]	Hadidi M, Karimabadi K, Ghanbari E, et al. Stem cells and exosomes: as biological agents in the diagnosis and treatment of polycystic ovary syndrome (PCOS)[J]. Front Endocrinol(Lausanne), 2023, 14:1269266. doi: 10.3389/fendo.2023.1269266.
[17]	Zheng X, Zhao D, Liu Y, et al. Regeneration and anti-inflammatory effects of stem cells and their extracellular vesicles in gynecological diseases[J]. Biomed Pharmacother, 2023, 168:115739. doi: 10.1016/j.biopha.2023.115739.
[18]	Zhao Y, Pan S, Li Y, et al. Exosomal miR-143-3p derived from follicular fluid promotes granulosa cell apoptosis by targeting BMPR1A in polycystic ovary syndrome[J]. Sci Rep, 2022, 12(1):4359. doi: 10.1038/s41598-022-08423-6.
[19]	赵元元, 吴小华. hUC-MSCs来源的外泌体miR-1260a影响PCOS患者颗粒细胞凋亡的研究[J]. 天津医药, 2023, 51(4):337-343. doi: 10.11958/20221070.
[20]	Cao M, Zhao Y, Chen T, et al. Adipose mesenchymal stem cell-derived exosomal microRNAs ameliorate polycystic ovary syndrome by protecting against metabolic disturbances[J]. Biomaterials, 2022, 288:121739. doi: 10.1016/j.biomaterials.2022.121739.
[21]	Park HS, Cetin E, Siblini H, et al. Therapeutic Potential of Mesenchymal Stem Cell-Derived Extracellular Vesicles to Treat PCOS[J]. Int J Mol Sci, 2023, 24(13):11151. doi: 10.3390/ijms241311151.
[22]	Stener-Victorin E, Teede H, Norman RJ, et al. Polycystic ovary syndrome[J]. Nat Rev Dis Primers, 2024, 10(1):27. doi: 10.1038/s41572-024-00511-3. pmid: 38637590
[23]	Wälchli-Popovic M, Monnerat S, Taylor AE, et al. Effects of interleukin-1 receptor antagonism in women with polycystic ovary syndrome-the FertIL trial[J]. Front Endocrinol(Lausanne), 2024, 15:1435698. doi: 10.3389/fendo.2024.1435698.
[24]	Xue Y, Lv J, Xu P, et al. Identification of microRNAs and genes associated with hyperandrogenism in the follicular fluid of women with polycystic ovary syndrome[J]. J Cell Biochem, 2018, 119(5):3913-3921. doi: 10.1002/jcb.26531. pmid: 29193229
[25]	Jiang X, Li J, Zhang B, et al. Differential expression profile of plasma exosomal microRNAs in women with polycystic ovary syndrome[J]. Fertil Steril, 2021, 115(3):782-792. doi: 10.1016/j.fertnstert.2020.08.019. pmid: 33041053
[26]	高琳芝, 谢云, 周怡, 等. M1型巨噬细胞源外泌体增强卵泡膜细胞的活力[J]. 中国病理生理杂志, 2020, 36(5):906-912. doi: 10.3969/j.issn.1000-4718.2020.05.020.
[27]	Li M, Gao S, Kang M, et al. Quercitrin alleviates lipid metabolism disorder in polycystic ovary syndrome-insulin resistance by upregulating PM20D1 in the PI3K/Akt pathway[J]. Phytomedicine, 2023, 117:154908. doi: 10.1016/j.phymed.2023.154908.
[28]	Stefanaki K, Karagiannakis DS, Peppa M, et al. Food Cravings and Obesity in Women with Polycystic Ovary Syndrome: Pathophysiological and Therapeutic Considerations[J]. Nutrients, 2024, 16(7):1049. doi: 10.3390/nu16071049.
[29]	Yan D, Song Y, Zhang B, et al. Progress and application of adipose-derived stem cells in the treatment of diabetes and its complications[J]. Stem Cell Res Ther, 2024, 15(1):3. doi: 10.1186/s13287-023-03620-0. pmid: 38167106
[30]	Hong Y, Wu J, Yu S, et al. Serum-Derived Exosomal microRNAs in Lipid Metabolism in Polycystic Ovary Syndrome[J]. Reprod Sci, 2022, 29(9):2625-2635. doi: 10.1007/s43032-022-00930-1. pmid: 35922742
[31]	Fang YQ, Zhang HK, Wei QQ, et al. Brown adipose tissue-derived exosomes improve polycystic ovary syndrome in mice via STAT3/GPX4 signaling pathway[J]. FASEB J, 2024, 38(18):e70062. doi: 10.1096/fj.202401346R.