From Vesicle Cargo to Cargo Selection in Obesity-Associated Polyendocrine Metabolic Ovarian Syndrome (PMOS)

In polycystic ovary syndrome (PCOS), recently renamed polyendocrine metabolic ovarian syndrome (PMOS), extracellular vesicle (EV) microRNA (miRNA) profiles differ from those of comparison groups, but those groups vary across studies. Lean healthy women, women with obesity and no PCOS and lean women with PCOS do not answer the same question, and lean healthy controls confound the syndrome with adiposity. Most work treats these miRNAs as biomarkers and leaves the prior question open: how an miRNA is selected for export. Selection is not passive. Sumoylated hnRNPA2B1 recognises GGAG motifs, YBX1 sorts miR-223 and other small non-coding RNAs, SYNCRIP binds an extra-seed motif and sorting sequences differ by cell type. Obesity alters the inputs to that step: adipose tissue is a major source of circulating exosomal miRNAs, its vesicles alter insulin sensitivity at a distance and gastric bypass changes their content. In the ovary, body mass index associates with EV-linked miRNAs in follicular fluid, and PCOS follicular exosomes carry miRNAs acting on granulosa cell apoptosis, senescence and glycolysis. Those effects are the readout of a loading step that, to our knowledge, has not been quantified in adipose tissue, serum, or follicular fluid of women with obesity-associated PCOS. Future work should measure hnRNPA2B1, YBX1 and SYNCRIP alongside EV miRNA profiles, with comparison groups that separate adiposity from diagnosis. Paired bariatric surgery samples offer one suitable design.