外泌体治疗卵巢早衰机制的研究进展
Research Progress on the Mechanisms of Exosome-Based Therapy for Premature Ovarian Failure
DOI: 10.12677/acm.2025.1551520, PDF,   
作者: 陈 杰：内蒙古医科大学内蒙古临床医学院，内蒙古 呼和浩特；马玉珍*：内蒙古自治区人民医院生殖医学科，内蒙古 呼和浩特
关键词: 卵巢早衰；外泌体；颗粒细胞；不孕；Premature Ovarian Failure； Exosomes； Granulosa Cell； Infertility
摘要: 卵巢早衰(Premature ovarian failure, POF)是一种近年发病率不断升高的妇科内分泌疾病，常导致不孕并伴随多种类似于更年期症状。目前POF病因暂不明确，治疗效果尚未达到预期，因此需要探索POF的新型治疗方式，改善卵巢功能，促进女性患者生育能力的恢复。外泌体广泛存在于血液、唾液、脑脊液等人体液体成分中，由脂质、蛋白质、RNA、DNA和其他与细胞来源相关的物质组成，介导细胞间的信息交流。大量研究表明，外泌体对于治疗卵巢疾病至关重要，可能作为重要靶点参与卵巢疾病的治疗过程，通过促进颗粒细胞功能恢复、促进卵巢再生、减少炎症、增强血管生成以及减轻氧化应激等各个方面对POF的治疗起到一定作用。现就当前外泌体对卵巢早衰的治疗作如下综述，以期为外泌体相关理论在POF的后续研究和治疗中提供参考。
Abstract: Premature ovarian failure (POF) is a gynecological endocrine disease with an increasing incidence in recent years. It often leads to infertility and is accompanied by various symptoms similar to those of menopause. Currently, the etiology of POF remains unclear, and the treatment effect has not yet met expectations. Therefore, it is necessary to explore new treatment methods for POF to improve ovarian function and promote the recovery of fertility in female patients. Exosomes are widely present in human body fluid components such as blood, saliva, and cerebrospinal fluid. They are composed of lipids, proteins, RNA, DNA, and other substances related to cell origin, and mediate intercellular communication. A large number of studies have shown that exosomes are crucial for the treatment of ovarian diseases. They may participate in the treatment process of ovarian diseases as important targets and play a certain role in the treatment of POF in various aspects, such as enhancement of granulosa cell functional recovery, promotion of ovarian regeneration, reduction of inflammation, augmentation of angiogenesis, and alleviation of oxidative stress. This article reviews the current treatment of premature ovarian failure with exosomes, aiming to provide a reference for the subsequent research and treatment of POF using exosome-related theories.
文章引用：陈杰, 马玉珍. 外泌体治疗卵巢早衰机制的研究进展[J]. 临床医学进展, 2025, 15(5): 1506-1513. https://doi.org/10.12677/acm.2025.1551520

参考文献

[1] Ke, H., Tang, S., Guo, T., Hou, D., Jiao, X., Li, S., et al. (2023) Landscape of Pathogenic Mutations in Premature Ovarian Insufficiency. Nature Medicine, 29, 483-492. [Google Scholar] [CrossRef] [PubMed]
[2] Wang, J., Sun, X., Yang, Z., Li, S., Wang, Y., Ren, R., et al. (2023) Epigenetic Regulation in Premature Ovarian Failure: A Literature Review. Frontiers in Physiology, 13, Article 998424. [Google Scholar] [CrossRef] [PubMed]
[3] Chu, K., He, Y., Li, Z., Jiang, Z., Wang, L., Ji, Y., et al. (2021) Novel LAT Pathogenic Variants in a POI Family and Its Role in the Ovary. Frontiers in Genetics, 12, Article 764160. [Google Scholar] [CrossRef] [PubMed]
[4] Liang, Q., Wang, Z., Lin, F., Zhang, C., Sun, H., Zhou, L., et al. (2018) Ablation of Beta Subunit of Protein Kinase CK2 in Mouse Oocytes Causes Follicle Atresia and Premature Ovarian Failure. Cell Death & Disease, 9, Article No. 508. [Google Scholar] [CrossRef] [PubMed]
[5] Touraine, P., Chabbert-Buffet, N., Plu-Bureau, G., Duranteau, L., Sinclair, A.H. and Tucker, E.J. (2024) Premature Ovarian Insufficiency. Nature Reviews Disease Primers, 10, Article No. 63. [Google Scholar] [CrossRef] [PubMed]
[6] Wu, X., Cai, H., Kallianpur, A., Li, H., Yang, G., Gao, J., et al. (2014) Impact of Premature Ovarian Failure on Mortality and Morbidity among Chinese Women. PLOS ONE, 9, e89597. [Google Scholar] [CrossRef] [PubMed]
[7] Lin, J., Wu, D., Jia, L., Liang, M., Liu, S., Qin, Z., et al. (2021) The Treatment of Complementary and Alternative Medicine on Premature Ovarian Failure. Evidence-Based Complementary and Alternative Medicine, 2021, Article ID: 6677767. [Google Scholar] [CrossRef] [PubMed]
[8] Craciunas, L., Zdoukopoulos, N., Vinayagam, S. and Mohiyiddeen, L. (2022) Hormone Therapy for Uterine and Endometrial Development in Women with Premature Ovarian Insufficiency. Cochrane Database of Systematic Reviews, No. 10, CD008209. [Google Scholar] [CrossRef] [PubMed]
[9] Rebar, R.W. (2009) Premature Ovarian Failure. Obstetrics & Gynecology, 113, 1355-1363. [Google Scholar] [CrossRef] [PubMed]
[10] Ishizuka, B. (2021) Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI). Frontiers in Endocrinology, 12, Article 626924. [Google Scholar] [CrossRef] [PubMed]
[11] Li, Q., Zheng, J., Li, Z., Xiao, Y., Zhang, M., Shi, W., et al. (2022) Drug-Free in vitro Activation Combined with 3D-Bioprinted Adipose-Derived Stem Cells Restores Ovarian Function of Rats with Premature Ovarian Insufficiency. Stem Cell Research & Therapy, 13, Article No. 347. [Google Scholar] [CrossRef] [PubMed]
[12] Sevgin, K. and Erguven, P. (2024) SIRT1 Overexpression by Melatonin and Resveratrol Combined Treatment Attenuates Premature Ovarian Failure through Activation of SIRT1/FOXO3a/BCL2 Pathway. Biochemical and Biophysical Research Communications, 696, Article 149506. [Google Scholar] [CrossRef] [PubMed]
[13] Shi, L., Zhang, Z., Deng, M., Zheng, F., Liu, W. and Ye, S. (2022) Biological Mechanisms and Applied Prospects of Mesenchymal Stem Cells in Premature Ovarian Failure. Medicine, 101, e30013. [Google Scholar] [CrossRef] [PubMed]
[14] Li, Z., Zhang, M., Tian, Y., Li, Q. and Huang, X. (2021) Mesenchymal Stem Cells in Premature Ovarian Insufficiency: Mechanisms and Prospects. Frontiers in Cell and Developmental Biology, 9, Article 718192. [Google Scholar] [CrossRef] [PubMed]
[15] Huang, Q., Chen, S., Chen, J., Shi, Q. and Lin, S. (2022) Therapeutic Options for Premature Ovarian Insufficiency: An Updated Review. Reproductive Biology and Endocrinology, 20, Article No. 28. [Google Scholar] [CrossRef] [PubMed]
[16] Kuchakzadeh, F., Ai, J. and Ebrahimi-Barough, S. (2024) Tissue Engineering and Stem Cell-Based Therapeutic Strategies for Premature Ovarian Insufficiency. Regenerative Therapy, 25, 10-23. [Google Scholar] [CrossRef] [PubMed]
[17] Yu, T., Chen, M., Lee, T., Chen, Y., Cheng, E., Huang, C., et al. (2025) Intraovarian Platelet-Rich Plasma Injection Significantly Improves Blastocyst Yield and Quality in IVF Patients. Scientific Reports, 15, Article No. 1301. [Google Scholar] [CrossRef] [PubMed]
[18] van der Pol, E., Böing, A.N., Harrison, P., Sturk, A. and Nieuwland, R. (2012) Classification, Functions, and Clinical Relevance of Extracellular Vesicles. Pharmacological Reviews, 64, 676-705. [Google Scholar] [CrossRef] [PubMed]
[19] Chen, Z. and Wang, X. (2022) The Role and Application of Exosomes and Their Cargos in Reproductive Diseases: A Systematic Review. Veterinary Sciences, 9, Article 706. [Google Scholar] [CrossRef] [PubMed]
[20] Kalluri, R. and LeBleu, V.S. (2020) The Biology, Function, and Biomedical Applications of Exosomes. Science, 367, eaau6977. [Google Scholar] [CrossRef] [PubMed]
[21] Lin, Y., Lu, Y. and Li, X. (2019) Biological Characteristics of Exosomes and Genetically Engineered Exosomes for the Targeted Delivery of Therapeutic Agents. Journal of Drug Targeting, 28, 129-141. [Google Scholar] [CrossRef] [PubMed]
[22] Chavda, V.P., Pandya, A., Kumar, L., Raval, N., Vora, L.K., Pulakkat, S., et al. (2023) Exosome Nanovesicles: A Potential Carrier for Therapeutic Delivery. Nano Today, 49, Article 101771. [Google Scholar] [CrossRef] 
[23] Reddy, P., Zheng, W. and Liu, K. (2010) Mechanisms Maintaining the Dormancy and Survival of Mammalian Primordial Follicles. Trends in Endocrinology & Metabolism, 21, 96-103. [Google Scholar] [CrossRef] [PubMed]
[24] Jiao, X., Zhang, X., Li, N., Zhang, D., Zhao, S., Dang, Y., et al. (2021) Treg Deficiency‐Mediated TH1 Response Causes Human Premature Ovarian Insufficiency through Apoptosis and Steroidogenesis Dysfunction of Granulosa Cells. Clinical and Translational Medicine, 11, e448. [Google Scholar] [CrossRef] [PubMed]
[25] Yang, M., Lin, L., Sha, C., Li, T., Zhao, D., Wei, H., et al. (2020) Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miR-144-5p Improves Rat Ovarian Function after Chemotherapy-Induced Ovarian Failure by Targeting PTEN. Laboratory Investigation, 100, 342-352. [Google Scholar] [CrossRef] [PubMed]
[26] Xiao, G., Cheng, C., Chiang, Y., Cheng, W.T., Liu, I. and Wu, S. (2016) Exosomal miR-10a Derived from Amniotic Fluid Stem Cells Preserves Ovarian Follicles after Chemotherapy. Scientific Reports, 6, Article No. 23120. [Google Scholar] [CrossRef] [PubMed]
[27] Cai, J., Sun, Y. and Bao, S. (2022) HucMSCs-Exosomes Containing miR-21 Promoted Estrogen Production in Ovarian Granulosa Cells via LATS1-Mediated Phosphorylation of LOXL2 and YAP. General and Comparative Endocrinology, 321, Article 114015. [Google Scholar] [CrossRef] [PubMed]
[28] Yu, Y.S., Sui, H.S., Han, Z.B., Li, W., Luo, M.J. and Tan, J.H. (2004) Apoptosis in Granulosa Cells during Follicular Atresia: Relationship with Steroids and Insulin-Like Growth Factors. Cell Research, 14, 341-346. [Google Scholar] [CrossRef] [PubMed]
[29] Gershon, E. and Dekel, N. (2020) Newly Identified Regulators of Ovarian Folliculogenesis and Ovulation. International Journal of Molecular Sciences, 21, Article 4565. [Google Scholar] [CrossRef] [PubMed]
[30] Li, Z., Zhang, M., Zheng, J., Tian, Y., Zhang, H., Tan, Y., et al. (2021) Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Improve Ovarian Function and Proliferation of Premature Ovarian Insufficiency by Regulating the Hippo Signaling Pathway. Frontiers in Endocrinology, 12, Article 711902. [Google Scholar] [CrossRef] [PubMed]
[31] Wang, L., Wang, L., Wang, R., Xu, T., Wang, J., Cui, Z., et al. (2024) Endometrial Stem Cell-Derived Exosomes Repair Cisplatin-Induced Premature Ovarian Failure via Hippo Signaling Pathway. Heliyon, 10, e31639. [Google Scholar] [CrossRef] [PubMed]
[32] Han, Y., Yao, R., Yang, Z., Li, S., Meng, W., Zhang, Y., et al. (2022) Interleukin-4 Activates the PI3K/AKT Signaling to Promote Apoptosis and Inhibit the Proliferation of Granulosa Cells. Experimental Cell Research, 412, Article 113002. [Google Scholar] [CrossRef] [PubMed]
[33] Ağaçayak, E., Yaman Görük, N., Küsen, H., Yaman Tunç, S., Başaranoğlu, S., İçen, M.S., et al. (2016) Role of Inflammation and Oxidative Stress in the Etiology of Primary Ovarian Insufficiency. Journal of Turkish Society of Obstetric and Gynecology, 13, 109-115. [Google Scholar] [CrossRef] [PubMed]
[34] Nazdikbin Yamchi, N., Ahmadian, S., Mobarak, H., Amjadi, F., Beheshti, R., Tamadon, A., et al. (2023) Amniotic Fluid-Derived Exosomes Attenuated Fibrotic Changes in POI Rats through Modulation of the TGF-β/Smads Signaling Pathway. Journal of Ovarian Research, 16, Article No. 118. [Google Scholar] [CrossRef] [PubMed]
[35] Bai, X. and Wang, S. (2022) Signaling Pathway Intervention in Premature Ovarian Failure. Frontiers in Medicine, 9, Article 999440. [Google Scholar] [CrossRef] [PubMed]
[36] Qu, Q., Liu, L., Cui, Y., Liu, H., Yi, J., Bing, W., et al. (2022) miR-126-3p Containing Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Promote Angiogenesis and Attenuate Ovarian Granulosa Cell Apoptosis in a Preclinical Rat Model of Premature Ovarian Failure. Stem Cell Research & Therapy, 13, Article No. 352. [Google Scholar] [CrossRef] [PubMed]
[37] Wang, Z., Tan, W., Li, B., Zou, J., Li, Y., Xiao, Y., et al. (2023) Exosomal Non-Coding RNAs in Angiogenesis: Functions, Mechanisms and Potential Clinical Applications. Heliyon, 9, e18626. [Google Scholar] [CrossRef] [PubMed]
[38] Khosravizadeh, Z., Rashidi, Z., Talebi, A., Khodamoradi, K. and Hassanzadeh, G. (2020) The Role of Mitochondria in Premature Ovarian Failure: A Review. Journal of Contemporary Medical Sciences, 6, 1-7. [Google Scholar] [CrossRef] 
[39] Ding, Y., Xia, B., Zhuo, G., Zhang, C. and Leng, J. (2019) Premature Ovarian Insufficiency May Be Associated with the Mutations in Mitochondrial tRNA Genes. Endocrine Journal, 66, 81-88. [Google Scholar] [CrossRef] [PubMed]
[40] Yang, G., Zhang, B., Xu, M., Wu, M., Lin, J., Luo, Z., et al. (2024) Improving Granulosa Cell Function in Premature Ovarian Failure with Umbilical Cord Mesenchymal Stromal Cell Exosome-Derived Hsa_circ_0002021. Tissue Engineering and Regenerative Medicine, 21, 897-914. [Google Scholar] [CrossRef] [PubMed]
[41] Zhu, X., Li, W., Lu, M., Shang, J., Zhou, J., Lin, L., et al. (2024) M6A Demethylase FTO-Stabilized Exosomal CircBRCA1 Alleviates Oxidative Stress-Induced Granulosa Cell Damage via the miR-642a-5p/FOXO1 Axis. Journal of Nanobiotechnology, 22, Article No. 367. [Google Scholar] [CrossRef] [PubMed]

为你推荐