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| Content Provider | frontiers |
|---|---|
| Author | Salehi, Reza Asare-Werehene, Meshach Wyse, Brandon A. Abedini, Atefeh Pan, Bo Gutsol, Alex Jahangiri, Sahar Szaraz, Peter Burns, Kevin D. Vanderhyden, Barbara Li, Julang Burger, Dylan Librach, Clifford L. Tsang, Benjamin K. |
| Abstract | Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenemia and ovarian antral follicle growth arrest. We have previously demonstrated that androgen-induced exosomal release of miR-379-5p (miR379) from preantral follicle granulosa cells increases the proliferation of target cells via phosphoinositide-dependent kinase 1 (PDK1) upregulation. Androgen also increases inflammatory M1 macrophage abundance, but reduces anti-inflammatory M2 polarization in rat antral and preovulatory follicles. However, the role of small extracellular vesicles (sEVs; also known as exosomes) secretion in determining the cellular content and function of miRNAs in exosome-receiving cells is largely unknown. Our objectives were to determine: 1) the regulatory role of granulosa cells (GC)-derived exosomal miR379 on macrophage polarization and ovarian inflammation; 2) whether miR379-induced M1 polarization regulates GC proliferation; and 3) if this regulated process is follicular stage-specific. Compared with non-PCOS subjects, PCOS subjects had a higher M1/M2 ratio, supporting the concept that PCOS is an inflammatory condition. Ovarian overexpression of miR379 increased the number of M1 macrophages and the M1/M2 ratio in preantral follicles specifically. Transfection of macrophages with a miR379 mimic reduced the cellular content of PDK1 and induced M0M1 polarization; whereas its inhibitor polarized M0M2. Conditioned media from macrophages transfected with miR379 mimic and follicular fluid from PCOS subjects had higher galectin-3 content, a pro-inflammatory cytokine which specifically suppresses human antral follicle GC proliferation. These results indicate that androgen-induced, GC-derived exosomal miR379 increases ovarian inflammation, a condition which suppresses GC proliferation in a follicle stage-dependent manner, as exhibited in PCOS. |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2023.1104550 |
| Volume Number | 14 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2023-03-24 |
| Access Restriction | Open |
| Subject Keyword | MiR-379-5p Macrophage PDK1 Extracellular vesicle PCOS (polycystic ovarian syndrome) Exosomes Granulosa Cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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