Advanced oxidation protein products change biological behaviors of rat endometrial epithelial cells by activating ERK/P38 signaling pathways

Advanced oxidation protein products (AOPPs) are a family of oxidized protein compounds and could induce oxidative stress and inflammatory lesion in various cells. The accumulation of AOPPs was associated with female reproductive diseases such as polycystic ovary syndrome (PCOS), leiomyoma and endometriosis. However, the relationship between AOPPs and endometrial cells is unclear. To explore the effects of accumulated AOPPs on endometrial cells, we treated normal rat endometrial epithelial cells (rEECs) and endometriosis model rats with AOPPs. Primary rEECs were collected from 8-week-old female Wistar rats. Increasing the amount of AOPPs in the media of rEECs enhanced rEEC proliferation and migration, and inhibited apoptosis. Moreover, AOPPs triggered the production of reactive oxygen species and nitrite along with activated ERK and P38 signal and this, in turn, led to an upregulation of proliferation and migration. With the treatment of antioxidants or the inhibitors of ERK and P38, the above effects of AOPPs on rEECs were attenuated. Additionally, in an endometriosis rat model, a similar phenomenon was observed in that the growth of endometriotic implants were promoted by AOPPs and EECs were significantly increased. This study indicated that the accumulation of AOPPs could promote rEEC proliferation and migration through ERK and P38 signal both in vivo and in vitro. This article has an associated First Person interview with the first author of the paper.