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This study highlights the molecular and functional distinctions between small (SEV) and large (LEV) FF EV subpopulations, revealing their specialised regulatory roles in granulosa cell (GC) biology and their consequential impact on ovarian function. Single\u2010EV profiling uncovered distinct tetraspanin distributions, with LEVs containing a lower proportion of CD9\/CD63\/CD81\u2010positive particles compared to SEVs. Fluorescent labelling confirmed uptake of both SEVs and LEVs by GCs, supporting their capacity to impact cellular behaviour. Functionally, LEVs increased testosterone production by GCs, whilst SEVs had no effect on steroid hormone secretion, suggesting a specific role for LEVs in androgen biosynthesis. Transcriptomic analysis revealed extensive SEV\u2010induced changes in GC gene expression, affecting pathways involved in transcription, TGF\u2010\u03b2 signalling, extracellular matrix (ECM) remodelling and cell cycle regulation. In contrast, LEVs elicited minimal transcriptional changes, primarily modulating genes associated with immune regulation and oxidative stress defence. Small RNA sequencing further revealed distinct non\u2010coding RNA (ncRNA) profiles, with SEVs enriched in miRNAs targeting pathways critical for GC differentiation, whilst LEVs carried higher levels of piRNAs implicated in maintaining genomic stability. These findings advance our understanding of FF EV\u2010mediated intercellular communication and underscore the importance of investigating EV subpopulations independently.<\/jats:p>","DOI":"10.1002\/jev2.70119","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T03:26:53Z","timestamp":1751858813000},"source":"Crossref","is-referenced-by-count":12,"title":["Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-1022","authenticated-orcid":false,"given":"Inge","family":"Varik","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biotechnology Tallinn University of Technology  Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7370-5463","authenticated-orcid":false,"given":"Katariina Johanna","family":"Saretok","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology Tallinn University of Technology  Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0504-2818","authenticated-orcid":false,"given":"Kristine","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology Tallinn University of Technology  Tallinn Estonia"},{"name":"Nova Vita Clinic  Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7040-1289","authenticated-orcid":false,"given":"Ileana","family":"Quintero","sequence":"additional","affiliation":[{"name":"HiPREP Core, Institute for Molecular Medicine Finland (FIMM) University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-1017","authenticated-orcid":false,"given":"Maija","family":"Puhka","sequence":"additional","affiliation":[{"name":"HiPREP Core, Institute for Molecular Medicine Finland (FIMM) University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1832-6116","authenticated-orcid":false,"given":"Nataliia","family":"Volkova","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology Tallinn University of Technology  Tallinn Estonia"},{"name":"Institute for Problems of Cryobiology and Cryomedicine National Academy of Sciences of Ukraine  Kharkiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Tro\u0161in","sequence":"additional","affiliation":[{"name":"East Tallinn Central Hospital  Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Guazzi","sequence":"additional","affiliation":[{"name":"HansaBioMed Life Sciences Ltd  Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1927-9016","authenticated-orcid":false,"given":"Agne","family":"Velthut\u2010Meikas","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biotechnology Tallinn University of Technology  Tallinn Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061445"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12551\u2010013\u20100124\u20100"},{"key":"e_1_2_11_5_1","unstructured":"Andrews S.2010.FastQC: A Quality Control Tool for High Throughput Sequence Data. 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