Objective To explore the effect of PIK3CA mutation on progesterone receptor expression in ovarian endometriosis and to provide evidences for exploring a new target for ovarian endometriosis treatment.

Methods Samples were collected from 48 ovarian endometriosis patients and 40 non-endometriosis controls underwent laparoscopic surgery in Nanjing Drum Tower Hospital, The Affiliated to Nanjing University Medical College between March 2020 to June 2022. Droplet digital polymerase chain reaction was used to detect PIK3CA mutations in ovarian endometriosis and normal endometrium. Immunohistochemical staining was used to detect expression levels and localization of PIK3CA and progesterone receptor in controls and ovarian endometriosis. mRNA levels of PIK3CA and progesterone receptor in controls and ovarian endometriosis were measured by quantitative real-time polymerase chain reaction. PIK3CA, Akt, and p-Akt protein levels were measured by Western Blotting in endometrial epithelial cells transfected with PIK3CA wild-type and mutant adenovirus.

Results PIK3CA mutations were detected in ovarian endometriosis epithelial cells while normal endometrium did not harbor this mutation. Compared with controls, PIK3CA protein and mRNA expression were increased in the epithelial tissues of ovarian endometriosis (all P < 0.05) while protein and mRNA expression of progesterone receptor were decreased (all P < 0.001), and expression of progesterone receptor were significantly decreased in PIK3CA positive group (all P < 0.001). PIK3CA mutation and overexpression in endometrial epithelial cells down-regulated the expression of progesterone receptor, and this down-regulated effect was more significant in the mutant group (all P < 0.05), but the activation of AKT pathway was lower than that in the overexpressed group.

Conclusions PIK3CA mutations may down-regulate progesterone receptor expression in epithelial cells of ovarian endometriosis via the nonclassical PI3K/Akt signaling pathway.