Follicular Fluid-Derived Small Extracellular Vesicles Alleviate DHEA-Induced Granulosa Cell Apoptosis by Delivering LINC00092

Polycystic ovary syndrome (PCOS) is a perplexing condition in females of reproductive age. Dysplasia of ovarian granulosa cell (GC) is implicated in PCOS. Follicular fluid (FF)-extracellular vesicles (Evs) are important in cell–cell communication during follicular development. The current study elaborated on the function and mechanism of FF-Evs in the viability and apoptosis of GC cells in PCOS development. Human GC cells KGN were treated with dehydroepiandrosterone (DHEA) to mimic a PCOS-like condition in vitro, which were further co-cultured with the FF-derived Evs (FF-Evs). The FF-Evs treatment significantly reduced DHEA-induced apoptosis of KGN cells while promoting cell viability and migration. The lncRNA microarray analysis showed that FF-Evs mainly deliver LINC00092 into the KGN cells. Knockdown of LINC00092 negated the protective effect of FF-Evs against DHEA-induced damage on KGN cells. Moreover, by performing bioinformatics analyses and biotin-labeled RNA pull-down assay, we found that LINC00092 could bind to the RNA binding protein LIN28B and inhibit its binding to pre-microRNA-18-5p, which allowed biogenesis of pre-miR-18-5p and increased the expression of miR-18b-5p, a miRNA with known alleviating role in PCOS by suppressing the PTEN mRNA. Collectively, the present work demonstrates that FF-Evs can alleviate DHEA-induced GC damage by delivering LINC00092. Graphical Abstract