Ovulation-derived extracellular vesicles exhibit sustained oncogenic influence on the exposed fallopian tube fimbrial cells after drainage into peritoneal cavity
Ovulation is known to damage fallopian tube epithelial (FTE) cells, promote cellular transformation, and contribute to the development of high-grade serous ovarian carcinoma (HGSC). While ovulatory follicular fluid-derived extracellular vesicles (EVs) have been shown to possess cell-transforming activity, it remains unclear whether these EVs persist in the peritoneal cavity after ovulation, potentially prolonging their exposure and enhancing their transformative effects on fallopian tube epithelial (FTE) cells. In this study, we collected follicular fluid (FF) and peritoneal fluid (PF) from women before and after ovulation, and investigated the oncogenic potential of ovulation-derived EVs on FTE cells using an anchorage-independent colony growth assay. We found that post-ovulatory PF exhibits significantly higher cell transformation activity compared to pre-ovulatory PF. This heightened activity correlates with an increased concentration of EVs and protein content in post-ovulatory PF. FF samples obtained from different ovulatory follicles of the same patient demonstrated consistent transformation activity, and FF- or post-ovulatory PF derived EVs retained this transforming capacity across FTE cells at varying stages of transformation. Our study reveals a novel mechanism by which ovulation may contribute to FTE transformation through the persistent oncogenic effects of EVs released into the peritoneal microenvironment. This finding provides new perspectives and directions for future cancer prevention, treatment, and potential diagnostic biomarker research.