Abstract

ABSTRACTAdvanced 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.

Highlights

  • Endometrial epithelial cells (EECs) are the major cell types in the endometrium

  • In endometriosis rats model, the similar phenomena was observed that the growth of endometriotic implants were promoted by Advanced oxidation protein products (AOPPs) and EECs were significantly increased

  • Increase in extracellular AOPPs was sufficient to trigger proliferation and migration, and block apoptosis of rats endometrial epithelial cells (rEECs) To explore the cells biological changes brought by AOPPs, cultured rEECs were incubated with indicted concentration of AOPP-modified rat serum albumin (RSA)

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Summary

Introduction

Endometrial epithelial cells (EECs) are the major cell types in the endometrium. The normal morphology and function of EECs plays a vital role in maintaining female reproductive health. In certain pathological conditions, the morphology of EECs is destroyed and its function is changed, such as excessive proliferation, invasion, epithelial-to-mesenchymal transition and fibrosis, which lead to the occurrence of reproductive diseases (Sun et al 2019; You et al 2019; An et al 2017; Meng et al 2019). In peritoneal fluid and follicular fluid of endometriosis, the level of AOPPs is extraordinarily high (Santulli et al, 2015; Song et al, 2018). These observations suggest that AOPPs accumulation has a close relationship with endometriosis, but it remains unknown whether AOPPs affect biological characteristics of EECs

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