Introduction Ovulation is the main cause of oncogenesis of fallopian tube epithelium (FTE), the origin of ovarian high-grade serous carcinoma (HGSC). Previously, we have identified multiple oncogenic activities of the ovulatory follicular fluid (FF), which exerts full-spectrum transforming activities on FTE cells. After ovulation, FF transfuses into the peritoneal fluid (PF) with which the FTE constantly bathes. We wonder whether PF exerts the same spectrum of oncogenic activities as FF and whether they are sourced from FF.

Methods By using a panel of FTE cells with p53 mutation (FT282-V), p53/CCNE1 aberrations (FT282-CCNE1), and after xenograft peritoneal metastasis after spontaneous transformation (FEXT2), we tested the change of different transformation phenotypes after treating with FF and PF collected before and after ovulation.

Results Similar to FF but to a lesser extent, PF generally promoted anchorage-independent growth (AIG), migration, anoikis resistance, and peritoneal attachment and invasion of the transforming FTE cells, and the more transformed cells were more affected. Activities of AIG, invasion, and peritoneal attachment growth were higher in luteal phase PF than proliferative PF, suggesting an ovulation source. In contrast, anoikis resistance and migration activities were indifferent between PF collected before and after ovulation, suggesting an ovulation-independent source. Finally, coinjection of Luc-FEXT2 cells with either FF or luteal phase PF, but not proliferative phase PF, supported early peritoneal implantation in NSG mice.

Conclusion/Implications PF from ovulating women promotes oncogenic phenotypes of FTE cells at different stages of malignant transformation. Other than anoikis resistance and cell migration, a majority of these activities are sourced from ovulation.