Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis.

Ning Chen,Hao Zhou,Zhenwei Xie,Juan Li,Fengxian Shen,Baoying Du,Shengtao Zhou

doi:10.1371/journal.pone.0182773

Abstract

ObjectiveTo explore the expression level of Nrf2 in adenomyosis and study the mechanism of abnormal expression of Nrf2 in the pathogenesis of adenomyosis.MethodsWestern blot, immunohistochemistry(IHC) and real time PCR were used to measure Nrf2 expression levels in tissue and cell samples. Knockdown and overexpression of Nrf2 were used to investigate the variation of migration ability of endometrial glandular cells as well as the regulatory mechanism.ResultsNrf2 protein levels were significantly higher in the eutopic and ectopic endometrial glands when compared with control cases using IHC and western blot methods. (p< 0.05). However, there was no statistical difference in Nrf2 mRNA expression levels between the adenomyosis and control groups. Using an agonist and Nrf2 siRNA, we regulated the Nrf2 protein levels of primary cultured endometrial glandular cells. With increased expression of Nrf2, cell scratch assay showed that the agonist-treated group migrated significantly faster than the control group, with MMP9 protein level markedly elevated. In contrast, Nrf2 siRNA-treated group migrated slower than the control group, with decreased expression of MMP9 protein. All of the scratching healing spaces and protein levels between the treated and control groups were statistically significant (p< 0.05).ConclusionsAbnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis. Specified reduction of Nrf2 expression could prove to be a new therapeutic target in the clinical treatment of adenomyosis.

Highlights

Adenomyosis is a common gynecological disorder, which is presented with a wide range of clinical presentations, such as heavy menstrual bleeding, dysmenorrhoea and infertility[1]
Nrf2 protein levels were significantly higher in the eutopic and ectopic endometrial glands when compared with control cases using IHC and western blot methods. (p< 0.05)
There was no statistical difference in Nrf2 mRNA expression levels between the adenomyosis and control groups

Summary

Introduction

Adenomyosis is a common gynecological disorder, which is presented with a wide range of clinical presentations, such as heavy menstrual bleeding, dysmenorrhoea and infertility[1]. The age of onset is getting younger and incidence is rising in recent years, the mechanism of pathogenesis of adenomyosis is still incompletely understood Both hysterectomy and many other kinds of conservative treatments can fail to completely relieve patient’s sufferings, and treatment options are especially limited for those planning for future pregnancies[2, 3]. There is an absence of submucousal layer between the basal endometrium and myometrium[4]. Iatrogenic injuries such as curettage, abortion, caesarean section and chronic inflammation may cause damage to the sub-endometrial myometrium. This is regarded as one of the key etiological factors of adenomyosis[5]. Damage and inflammation bring forth increased oxygen uptake, leading to an increased release and accumulation of ROS at the site of damage[6]

Methods

Results

Conclusion