Adipocytes-Derived Extracellular Vesicle-miR-26b Promotes Apoptosis of Cumulus Cells and Induces Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is a refractory reproductive disease and also a kind of endocrine and metabolic disease. Adipocyte cells can produce a mass of extracellular vesicles and orchestrate the status of other types cells. The objective of this study was to determine the effects of adipocyte-derived extracellular vesicles-miR-26b on cumulus cells (CCs) and development of PCOS.

Methods: The crosstalk mediated by extracellular vesicle-miR-26b between adipocytes and CCs was determined in CC cells co-cultured with mature adipocytes or incubated with extracellular vesicle isolated from mature adipocytes. CCK-8 assay and flow cytometry were conducted in CCs treated with or without extracellular vesicles; microRNA (miRNA) sequencing was conducted for clarifying the key molecular. Hormone levels and ovary ovulation ability were conducted with animal experiment.

Results: The results revealed that miR-26b was upregulated in extracellular vesicles derived from mature adipocytes. Adipocyte-derived extracellular vesicles inhibited viability and promoted apoptosis in CCs targeting JAG1. Furthermore, extracellular vesicles derived from mature adipocyte disrupted the ovary ovulation and impaired the hormone levels.

Conclusions: These results identify a novel signaling pathway that adipocytes-derived extracellular vesicles-miR-26b promotes cell apoptosis in CCs and disrupted the ovary ovulation in the development of PCOS. The study indicates that adipose tissue-derived extracellular vesicles-miR-26b may play a key role in the PCOS and also provides insight into developing new therapeutic strategies for PCOS.