Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells
ABSTRACT Follicular fluid extracellular vesicles (FF EVs) facilitate communication between oocytes and somatic cells within the ovarian follicle, playing a pivotal role in follicular development. This study highlights the molecular and functional distinctions between small (SEV) and large (LEV) FF E...
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| Format: | Article |
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Wiley
2025-07-01
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| Series: | Journal of Extracellular Vesicles |
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| Online Access: | https://doi.org/10.1002/jev2.70119 |
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| author | Inge Varik Katariina Johanna Saretok Kristine Rosenberg Ileana Quintero Maija Puhka Nataliia Volkova Aleksander Trošin Paolo Guazzi Agne Velthut‐Meikas |
| author_facet | Inge Varik Katariina Johanna Saretok Kristine Rosenberg Ileana Quintero Maija Puhka Nataliia Volkova Aleksander Trošin Paolo Guazzi Agne Velthut‐Meikas |
| author_sort | Inge Varik |
| collection | DOAJ |
| description | ABSTRACT Follicular fluid extracellular vesicles (FF EVs) facilitate communication between oocytes and somatic cells within the ovarian follicle, playing a pivotal role in follicular development. 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‐EV profiling uncovered distinct tetraspanin distributions, with LEVs containing a lower proportion of CD9/CD63/CD81‐positive 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‐induced changes in GC gene expression, affecting pathways involved in transcription, TGF‐β 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‐coding 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‐mediated intercellular communication and underscore the importance of investigating EV subpopulations independently. |
| format | Article |
| id | doaj-art-3eb85d103dae43f1aa96afeb00d91587 |
| institution | Kabale University |
| issn | 2001-3078 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj-art-3eb85d103dae43f1aa96afeb00d915872025-08-20T03:56:49ZengWileyJournal of Extracellular Vesicles2001-30782025-07-01147n/an/a10.1002/jev2.70119Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa CellsInge Varik0Katariina Johanna Saretok1Kristine Rosenberg2Ileana Quintero3Maija Puhka4Nataliia Volkova5Aleksander Trošin6Paolo Guazzi7Agne Velthut‐Meikas8Department of Chemistry and Biotechnology Tallinn University of Technology Tallinn EstoniaDepartment of Chemistry and Biotechnology Tallinn University of Technology Tallinn EstoniaDepartment of Chemistry and Biotechnology Tallinn University of Technology Tallinn EstoniaHiPREP Core, Institute for Molecular Medicine Finland (FIMM) University of Helsinki Helsinki FinlandHiPREP Core, Institute for Molecular Medicine Finland (FIMM) University of Helsinki Helsinki FinlandDepartment of Chemistry and Biotechnology Tallinn University of Technology Tallinn EstoniaEast Tallinn Central Hospital Tallinn EstoniaHansaBioMed Life Sciences Ltd Tallinn EstoniaDepartment of Chemistry and Biotechnology Tallinn University of Technology Tallinn EstoniaABSTRACT Follicular fluid extracellular vesicles (FF EVs) facilitate communication between oocytes and somatic cells within the ovarian follicle, playing a pivotal role in follicular development. 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‐EV profiling uncovered distinct tetraspanin distributions, with LEVs containing a lower proportion of CD9/CD63/CD81‐positive 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‐induced changes in GC gene expression, affecting pathways involved in transcription, TGF‐β 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‐coding 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‐mediated intercellular communication and underscore the importance of investigating EV subpopulations independently.https://doi.org/10.1002/jev2.70119extracellular vesiclesfollicular fluidgranulosa cellsmiRNAncRNAovary |
| spellingShingle | Inge Varik Katariina Johanna Saretok Kristine Rosenberg Ileana Quintero Maija Puhka Nataliia Volkova Aleksander Trošin Paolo Guazzi Agne Velthut‐Meikas Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells Journal of Extracellular Vesicles extracellular vesicles follicular fluid granulosa cells miRNA ncRNA ovary |
| title | Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells |
| title_full | Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells |
| title_fullStr | Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells |
| title_full_unstemmed | Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells |
| title_short | Small and Large Extracellular Vesicles From Human Preovulatory Follicular Fluid Display Distinct ncRNA Cargo Profiles and Differential Effects on KGN Granulosa Cells |
| title_sort | small and large extracellular vesicles from human preovulatory follicular fluid display distinct ncrna cargo profiles and differential effects on kgn granulosa cells |
| topic | extracellular vesicles follicular fluid granulosa cells miRNA ncRNA ovary |
| url | https://doi.org/10.1002/jev2.70119 |
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