{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:07:52Z","timestamp":1788901672647,"version":"build-2803163510"},"reference-count":96,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2014such as miR-21, miR-34c, miR-143-3p, miR-155-5p, miR-339-5p, and miR-424-5p\u2014were identified as regulators of critical pathways including phosphoinositide 3-kinase (PI3K)\u2013AKT, ERK1\/2, TGF-\u03b2\/SMAD, and Rb\u2013E2F1. 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.<\/jats:p>","DOI":"10.3390\/ijms26115363","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T11:55:52Z","timestamp":1748951752000},"page":"5363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Exosomal Communication Between Cumulus\u2013Oocyte Complexes and Granulosa Cells: A New Molecular Axis for Oocyte Competence in Human-Assisted Reproduction"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9477-7619","authenticated-orcid":false,"given":"Charalampos","family":"Voros","sequence":"first","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diamantis","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"IVF Athens Reproduction Center V. Athanasiou, 15123 Maroussi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1220-6594","authenticated-orcid":false,"given":"Despoina","family":"Mavrogianni","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8725-7103","authenticated-orcid":false,"given":"Antonia","family":"Varthaliti","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriakos","family":"Bananis","sequence":"additional","affiliation":[{"name":"King\u2019s College Hospitals NHS Foundation Trust, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"IVF Athens Reproduction Center V. Athanasiou, 15123 Maroussi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Athanasiou","sequence":"additional","affiliation":[{"name":"IVF Athens Reproduction Center V. Athanasiou, 15123 Maroussi, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Papadimas","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1376-7895","authenticated-orcid":false,"given":"Athanasios","family":"Gkirgkinoudis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-5054","authenticated-orcid":false,"given":"Ioannis","family":"Papapanagiotou","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriaki","family":"Migklis","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Vaitsis","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristotelis-Marios","family":"Koulakmanidis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris","family":"Mazis Kourakos","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Ivanidou","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Anastasia","family":"Daskalaki","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-7796","authenticated-orcid":false,"given":"Marianna","family":"Theodora","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-5922","authenticated-orcid":false,"given":"Panagiotis","family":"Antsaklis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8686-594X","authenticated-orcid":false,"given":"Dimitrios","family":"Loutradis","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"},{"name":"Fertility Institute-Assisted Reproduction Unit, Paster 15, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-211X","authenticated-orcid":false,"given":"Georgios","family":"Daskalakis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 VasilissisSofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1342905","DOI":"10.3389\/fcell.2024.1342905","article-title":"How great thou ART: Biomechanical properties of oocytes and embryos as indicators of quality in assisted reproductive technologies","volume":"12","author":"Fluks","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1152\/physrev.00032.2022","article-title":"Making a good egg: Human oocyte health, aging, and in vitro development","volume":"103","author":"Telfer","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Orozco-Galindo, B.V., S\u00e1nchez-Ram\u00edrez, B., Gonz\u00e1lez-Trevizo, C.L., Castro-Valenzuela, B., Varela-Rodr\u00edguez, L., and Burrola-Barraza, M.E. (2025). Folliculogenesis: A Cellular Crosstalk Mechanism. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47020113"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1021\/acs.jproteome.8b00647","article-title":"Quantitative Proteomic Analysis of Small and Large Extracellular Vesicles (EVs) Reveals Enrichment of Adhesion Proteins in Small EVs","volume":"18","author":"Jimenez","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.omtn.2022.04.011","article-title":"Microfluidics for detection of exosomes and microRNAs in cancer: State of the art","volume":"28","author":"Mousavi","year":"2022","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Di Bella, M.A. (2022). Overview and Update on Extracellular Vesicles: Considerations on Exosomes and Their Application in Modern Medicine. Biology, 11.","DOI":"10.3390\/biology11060804"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1186\/s13048-024-01551-9","article-title":"Unraveling the complexity of follicular fluid: Insights into its composition, function, and clinical implications","volume":"17","author":"Pan","year":"2024","journal-title":"J. Ovarian Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17036","DOI":"10.1038\/s41598-018-35379-3","article-title":"Extracellular microRNAs profile in human follicular fluid and IVF outcomes","volume":"8","author":"Martinez","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1186\/s12958-022-00989-0","article-title":"MicroRNAs secreted by human preimplantation embryos and IVF outcome","volume":"20","author":"Kamijo","year":"2022","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Iliescu, F.S., Vrta\u010dnik, D., Neuzil, P., and Iliescu, C. (2019). Microfluidic Technology for Clinical Applications of Exosomes. Micromachines, 10.","DOI":"10.3390\/mi10060392"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.fertnstert.2014.08.005","article-title":"Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: Bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation","volume":"102","author":"Santonocito","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Krylova, S.V., and Feng, D. (2023). The Machinery of Exosomes: Biogenesis, Release, and Uptake. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021337"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3109\/10409238.2014.881777","article-title":"The ESCRT machinery: From the plasma membrane to endosomes and back again","volume":"49","author":"Schuh","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/j.devcel.2021.03.020","article-title":"Extracellular vesicles: Critical players during cell migration","volume":"56","author":"Sung","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41580-023-00576-0","article-title":"Context-specific regulation of extracellular vesicle biogenesis and cargo selection","volume":"24","author":"Dixson","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: Small RNAs with a big role in gene regulation","volume":"5","author":"He","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S243","DOI":"10.21037\/tcr.2017.10.46","article-title":"Exosomal lncRNAs as new players in cell-to-cell communication","volume":"7","author":"Dragomir","year":"2018","journal-title":"Transl. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.semcancer.2021.07.014","article-title":"Heat shock proteins and exosomes in cancer theranostics","volume":"86","author":"Regimbeau","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1095\/biolreprod.115.132977","article-title":"Extracellular Vesicles from Bovine Follicular Fluid Support Cumulus Expansion1","volume":"93","author":"Hung","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e78505","DOI":"10.1371\/journal.pone.0078505","article-title":"Exosomal and Non-Exosomal Transport of Extra-Cellular microRNAs in Follicular Fluid: Implications for Bovine Oocyte Developmental Competence","volume":"8","author":"Sohel","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"gaae019","DOI":"10.1093\/molehr\/gaae019","article-title":"Extracellular vesicles secreted by cumulus cells contain microRNAs that are potential regulatory factors of mouse oocyte developmental competence","volume":"30","author":"Fiorentino","year":"2024","journal-title":"Mol. Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fendo.2018.00402","article-title":"Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation","volume":"9","author":"Hayder","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/ni.1784","article-title":"The cunning little vixen: Foxo and the cycle of life and death","volume":"10","author":"Hedrick","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-022-01257-8","article-title":"The sirtuin family in health and disease","volume":"7","author":"Wu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4015874","DOI":"10.1155\/2017\/4015874","article-title":"Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage","volume":"2017","author":"Mihalas","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ydbio.2021.08.008","article-title":"MicroRNA-21 is involved in oocyte maturation, blastocyst formation, and pre-implantation embryo development","volume":"480","author":"Dehghan","year":"2021","journal-title":"Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1038\/s41598-023-28686-x","article-title":"Evaluation of the potential of miR-21 as a diagnostic marker for oocyte maturity and embryo quality in women undergoing ICSI","volume":"13","author":"Jenabi","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1477-7827-4-21","article-title":"Smad signalling in the ovary","volume":"4","author":"Jeffery","year":"2006","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/humupd\/dml062","article-title":"Molecular mechanisms of ovulation: Co-ordination through the cumulus complex","volume":"13","author":"Russell","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1007\/s10815-020-01860-0","article-title":"Extracellular microRNA profiling in human follicular fluid: New biomarkers in female reproductive potential","volume":"37","author":"Qasemi","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1073\/pnas.0910667107","article-title":"Targeting of SMAD5 links microRNA-155 to the TGF-\u03b2 pathway and lymphomagenesis","volume":"107","author":"Rai","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1055\/s-2006-948551","article-title":"Extracellular Matrix of the Cumulus-Oocyte Complex","volume":"24","author":"Russell","year":"2006","journal-title":"Semin. Reprod. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/humupd\/dmaa043","article-title":"Metabolic co-dependence of the oocyte and cumulus cells: Essential role in determining oocyte developmental competence","volume":"27","author":"Richani","year":"2020","journal-title":"Hum. Reprod. Updat."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Liu, S., Jia, Y., Meng, S., Luo, Y., Yang, Q., and Pan, Z. (2023). Mechanisms of and Potential Medications for Oxidative Stress in Ovarian Granulosa Cells: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119205"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"929677","DOI":"10.3389\/fimmu.2022.929677","article-title":"miR-aculous new avenues for cancer immunotherapy","volume":"13","author":"Tang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.lfs.2016.08.028","article-title":"miR-15a\/miR-16 induces mitochondrial dependent apoptosis in breast cancer cells by suppressing oncogene BMI1","volume":"164","author":"Patel","year":"2016","journal-title":"Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chico-Sordo, L., and Garc\u00eda-Velasco, J.A. (2024). MicroRNAs as Biomarkers and Therapeutic Targets in Female Infertility. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312979"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1530\/REP-17-0157","article-title":"miR-15a-5p levels correlate with poor ovarian response in human follicular fluid","volume":"154","author":"Zhang","year":"2017","journal-title":"Reproduction"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhang, C.-H., Liu, X.-Y., and Wang, J. (2023). Essential Role of Granulosa Cell Glucose and Lipid Metabolism on Oocytes and the Potential Metabolic Imbalance in Polycystic Ovary Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216247"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1279469","DOI":"10.3389\/fphys.2023.1279469","article-title":"The physiological functions and therapeutic potential of exosomes during the development and treatment of polycystic ovary syndrome","volume":"14","author":"Zhang","year":"2023","journal-title":"Front. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"809596","DOI":"10.3389\/fendo.2022.809596","article-title":"The Role of Extracellular Vesicles in Embryo Implantation","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s13048-024-01480-7","article-title":"Extracellular vesicles and their content in the context of polycystic ovarian syndrome and endometriosis: A review","volume":"17","author":"Duval","year":"2024","journal-title":"J. Ovarian Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"725","DOI":"10.18632\/aging.100603","article-title":"Age-related changes in microRNA levels in serum","volume":"5","author":"Fitzpatrick","year":"2013","journal-title":"Aging"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12920-023-01756-9","article-title":"Specific expression profile of follicular fluid-derived exosomal microRNAs in patients with diminished ovarian reserve","volume":"16","author":"Shen","year":"2023","journal-title":"BMC Med. Genom."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s40104-024-01059-8","article-title":"From follicle to blastocyst: microRNA-34c from follicular fluid-derived extracellular vesicles modulates blastocyst quality","volume":"15","author":"Benedetti","year":"2024","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12964-022-00876-6","article-title":"Follicular fluid-derived exosomal miR-143-3p\/miR-155-5p regulate follicular dysplasia by modulating glycolysis in granulosa cells in polycystic ovary syndrome","volume":"20","author":"Cao","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"110030","DOI":"10.1016\/j.cellsig.2021.110030","article-title":"PCOS follicular fluid derived exosomal miR-424-5p induces granulosa cells senescence by targeting CDCA4 expression","volume":"85","author":"Yuan","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.theriogenology.2024.04.022","article-title":"Follicular fluid exosome-derived miR-339-5p enhances in vitro maturation of porcine oocytes via targeting SFPQ, a regulator of the ERK1\/2 pathway","volume":"225","author":"Han","year":"2024","journal-title":"Theriogenology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13048-025-01619-0","article-title":"Correlation between the follicular fluid extracellular-vesicle-derived microRNAs and signaling disturbance in the oocytes of women with polycystic ovary syndrome","volume":"18","author":"Liao","year":"2025","journal-title":"J. Ovarian Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12929-023-00964-w","article-title":"Exosomal miRNA-mediated intercellular communications and immunomodulatory effects in tumor microenvironments","volume":"30","author":"Nail","year":"2023","journal-title":"J. Biomed. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/biolre\/ioae081","article-title":"Mapping the follicle-specific regulation of extracellular vesicle-mediated microRNA transport in the southern white rhinoceros (Ceratotherium simum simum)","volume":"111","author":"Gad","year":"2024","journal-title":"Biol. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1002\/JLB.2MIR0817-349R","article-title":"The PI3K\/AKT signaling pathway in regulatory T-cell development, stability, and function","volume":"103","author":"Pompura","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.reprotox.2020.12.001","article-title":"Effects of bisphenol A and bisphenol S on microRNA expression during bovine (Bos taurus) oocyte maturation and early embryo development","volume":"99","author":"Sabry","year":"2021","journal-title":"Reprod. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"954","DOI":"10.18632\/oncotarget.652","article-title":"Mutations and Deregulation of Ras\/Raf\/MEK\/ERK and PI3K\/PTEN\/Akt\/mTOR Cascades Which Alter Therapy Response","volume":"3","author":"McCubrey","year":"2012","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"998","DOI":"10.12688\/f1000research.17196.1","article-title":"mTOR as a central regulator of lifespan and aging","volume":"8","author":"Papadopoli","year":"2019","journal-title":"F1000Research"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1095\/biolreprod.114.127274","article-title":"Activation of Mouse Cumulus-Oocyte Complex Maturation In Vitro Through EGF-Like Activity of Versican1","volume":"92","author":"Dunning","year":"2015","journal-title":"Biol. Reprod."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ncrna.2025.05.002","article-title":"The emerging role of miRNAs in biological aging and age-related diseases","volume":"13","author":"Turko","year":"2025","journal-title":"Non-Coding RNA Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1002\/mrd.22581","article-title":"Long non-coding RNA regulation of reproduction and development","volume":"82","author":"Taylor","year":"2015","journal-title":"Mol. Reprod. Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"106841","DOI":"10.1016\/j.phrs.2023.106841","article-title":"Role of hypoxia in cellular senescence","volume":"194","author":"Gao","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13048-024-01427-y","article-title":"Ovarian aging: Energy metabolism of oocytes","volume":"17","author":"Bao","year":"2024","journal-title":"J. Ovarian Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"171774","DOI":"10.1016\/j.scitotenv.2024.171774","article-title":"Environmental pollutants and exosomes: A new paradigm in environmental health and disease","volume":"925","author":"Salahshoori","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40001-023-01586-6","article-title":"Metabolomic profiling of exosomes reveals age-related changes in ovarian follicular fluid","volume":"29","author":"Gu","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1210\/jc.2013-1715","article-title":"Identification of MicroRNAs in Human Follicular Fluid: Characterization of MicroRNAs That Govern Steroidogenesis in Vitro and Are Associated With Polycystic Ovary Syndrome in Vivo","volume":"98","author":"Sang","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_67","first-page":"3984937","article-title":"MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans","volume":"2016","author":"Kubista","year":"2015","journal-title":"Stem Cells Int."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Szczepanek, J., and Tretyn, A. (2023). MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications. Biomolecules, 13.","DOI":"10.3390\/biom13111590"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Gabry\u015b, J., Gurgul, A., Szmato\u0142a, T., Kij-Mitka, B., Andronowska, A., Karnas, E., Kucharski, M., Wojciechowska-Pucha\u0142ka, J., Kochan, J., and Bugno-Poniewierska, M. (2024). Correction: Gabry\u015b et al. Follicular Fluid-Derived Extracellular Vesicles Influence on In Vitro Maturation of Equine Oocyte: Impact on Cumulus Cell Viability, Expansion and Transcriptome. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063262"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"dvaa009","DOI":"10.1093\/eep\/dvaa009","article-title":"Transgenerational epigenetic reprogramming of early embryos: A mechanistic model","volume":"6","author":"Spadafora","year":"2020","journal-title":"Environ. Epigenetics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"108047","DOI":"10.1016\/j.jbc.2024.108047","article-title":"The signaling landscape of insulin-like growth factor 1","volume":"301","author":"Khan","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s13046-018-0898-9","article-title":"Regulation of PTEN expression by noncoding RNAs","volume":"37","author":"Li","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41392-021-00646-9","article-title":"Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: The regulation and intervention","volume":"6","author":"Zhu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Park, H.J., Kim, B., Koo, D.B., and Lee, D.S. (2021). Peroxiredoxin 1 Controls Ovulation and Ovulated Cumulus\u2013Oocyte Complex Activity through TLR4-Derived ERK1\/2 Signaling in Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179437"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1439-0531.2010.01739.x","article-title":"The Role of Oocyte-Secreted Factors GDF9 and BMP15 in Follicular Development and Oogenesis","volume":"46","author":"Paulini","year":"2010","journal-title":"Reprod. Domest. Anim."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Del Bianco, D., Gentile, R., Sallicandro, L., Biagini, A., Quellari, P.T., Gliozheni, E., Sabbatini, P., Ragonese, F., Malvasi, A., and D\u2019amato, A. (2024). Electro-Metabolic Coupling of Cumulus\u2013Oocyte Complex. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105349"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ov\u010dar, A., and Kova\u010di\u010d, B. (2024). Biogenesis of Extracellular Vesicles (EVs) and the Potential Use of Embryo-Derived EVs in Medically Assisted Reproduction. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010042"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/humupd\/dmx040","article-title":"Acquisition of oocyte competence to develop as an embryo: Integrated nuclear and cytoplasmic events","volume":"24","author":"Conti","year":"2018","journal-title":"Hum. Reprod. Updat."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e70041","DOI":"10.1002\/jex2.70041","article-title":"Extracellular Vesicles From Follicular Fluid in Infertile Women: Size, Morphology and miRNA Content Analysis","volume":"4","author":"Ducarre","year":"2025","journal-title":"J. Extracell. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/s41392-024-01888-z","article-title":"Cell\u2013cell communication: New insights and clinical implications","volume":"9","author":"Su","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jare.2024.01.025","article-title":"Core fucosylation regulates the ovarian response via FSH receptor during follicular development","volume":"67","author":"Wang","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s13238-018-0603-y","article-title":"Loss-of-function of sox3 causes follicle development retardation and reduces fecundity in zebrafish","volume":"10","author":"Hong","year":"2018","journal-title":"Protein Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/humupd\/dmu036","article-title":"The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders","volume":"20","author":"Persani","year":"2014","journal-title":"Hum. Reprod. Updat."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s10815-020-02019-7","article-title":"The role of miRNAs in polycystic ovary syndrome with insulin resistance","volume":"38","author":"Luo","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.15252\/embj.201489589","article-title":"Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T-cell differentiation","volume":"34","author":"Warth","year":"2015","journal-title":"EMBO J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"639","DOI":"10.18502\/ijrm.v22i8.17237","article-title":"The possible regulatory role of miR-4463 and its target gene CYP19A1 on the ovarian response in the women with diminished ovarian reserve: A case-control study","volume":"22","author":"Yazdanian","year":"2024","journal-title":"Int. J. Reprod. Biomed. (IJRM)"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.trsl.2022.07.007","article-title":"Role and mechanism of miR-335-5p in the pathogenesis and treatment of polycystic ovary syndrome","volume":"252","author":"Zhang","year":"2022","journal-title":"Transl. Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Cammarata, G., Barraco, N., Giusti, I., Gristina, V., Dolo, V., and Taverna, S. (2022). Extracellular Vesicles-ceRNAs as Ovarian Cancer Bi-omarkers: Looking into circRNA-miRNA-mRNA Code. Cancers, 14.","DOI":"10.3390\/cancers14143404"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"101694","DOI":"10.1016\/j.pneurobio.2019.101694","article-title":"Exosomal miRNAs in central nervous system diseases: Biomarkers, pathological mediators, protective factors and therapeutic agents","volume":"183","author":"Xia","year":"2019","journal-title":"Prog. Neurobiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1387\/ijdb.120133cc","article-title":"The antral follicle: A microenvironment for oocyte differentiation","volume":"56","author":"Hennet","year":"2012","journal-title":"Int. J. Dev. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Yan, B., and Liang, Y. (2022). New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415758"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Wu, X., Meng, Y., Yao, Z., Lin, X., Hu, M., Cai, S., Gao, S., and Zhang, H. (2025). Extracellular vesicles as nature\u2019s nano carriers in cancer therapy: Insights toward preclinical studies and clinical applications. Pharmacol. Res., 107751.","DOI":"10.1016\/j.phrs.2025.107751"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4141","DOI":"10.1039\/D0CS00609B","article-title":"Advances in multiplexed techniques for the detection and quantification of microRNAs","volume":"50","author":"Jet","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/978-3-319-31973-5_8","article-title":"Control of Oocyte Growth and Development by Intercellular Communication Within the Follicular Niche","volume":"Volume 58","author":"Piprek","year":"2016","journal-title":"Molecular Mechanisms of Cell Differentiation in Gonad Development"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s10571-015-0293-4","article-title":"Extracellular Vesicles and MicroRNAs: Their Role in Tumorigenicity and Therapy for Brain Tumors","volume":"36","author":"Bronisz","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1186\/s13048-024-01542-w","article-title":"Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA","volume":"17","author":"Cui","year":"2024","journal-title":"J. Ovarian Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5363\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:46:44Z","timestamp":1760032004000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,3]]},"references-count":96,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115363"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115363","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,3]]}}}