Expression of SOX2, NANOG and OCT4 in a mouse model of lipopolysaccharide-induced acute uterine injury and intrauterine adhesions

Abstract

BackgroundActivation of inflammation-mediated endometrial injury is suggested to play a decisive role in pathogenesis of intrauterine adhesion (IUA). The stem cell theory of endometrial diseases has been given a hotspot, in that human endometrial stem cells have been isolated from the endometrium. Three transcription factors that play key roles in maintaining pluripotency and self-renewal in stem cells are sex-determining region Y-box2 (SOX2), Nanog homebox (NANOG), and octamer-binding protein (OCT4), which may be responsible for the damage or repair process of uterine endometrium. We aim to investigate the expression of SOX2, NANOG and OCT4 in a mouse model of acute uterine injury induced by peritoneal injection of lipopolysaccharide (LPS) and also analyze their changes in endometrium of women with IUA.MethodsThe mouse uterine horns were collected at 0 h, 6 h, 12 h, 18 h or 24 h after a single dose of LPS or PBS injection. Meanwhile, we recruited 19 women with IUA diagnosed by hysteroscopy and 16 disease-free women as control group. Endometrial tissue samples were collected. SOX2, NANOG, and OCT4 expression were analyzed with Quantitative Real-time Polymerase Chain Reaction and Western blotting assay.ResultsIn a mouse model of acute uterine injury, there was significant upregulation of NANOG at 6 h, SOX2 and OCT4 at 12 h compared with the values before injection or PBS injection. NANOG expression reached a peak at 6 h, while SOX2 and OCT4 peaked later at 12 h after LPS treatment. NANOG mRNA and protein expressions were significantly higher in endometrium of IUA patients compared to those of the control group.ConclusionsExpression of pluripotency factors SOX2, NANOG and OCT4 increased in a mouse model of LPS-induced acute uterine injury. NANOG peaked earlier followed by the other two factors before returning to baseline levels. NANOG but not SOX2 and OCT4 expression was overexpressed in the endometrium of women with IUA. They may be involved in the formation or restoration of IUA, and their roles in pathogenesis of IUA need to be further studied.

Platelet-rich plasma improves therapeutic effects of menstrual blood-derived stromal cells in rat model of intrauterine adhesion

“…Inflammation has been suggested to hinder the recovery of injured endometrium and proven to be an important procedure involved in the deposition of fibrotic tissue in intrauterine adhesions [35]. Simultaneously, transcription factor nuclear factor-kappaB (NF-κB), which promotes the expression of inflammatory cytokines and plays an essential role in inflammatory diseases, was confirmed to be significantly elevated in endometrial samples from IUA patients and animal model [36].…”

Correlation of Cancer Stem-Cell Markers OCT4, SOX2, and NANOG with Clinicopathological Features and Prognosis in Operative Patients with Rectal Cancer

“…SOX2 [located on chromosome 3 (3p181.71)] and NANOG [located on chromosome 12 (12p13.31)] are responsible for regulating the pluripotency and self-renewal of stem cells. 32 33 Both of them have been identified to play critical roles in multiple processes during tumorigenesis and tumor development in various malignant tumors, such as lung cancer, breast cancer, and endometrial cancer. 34 35 Whole blood SOX2 has been shown to be positively associated with lymph node metastasis, and SOX2 expression predicts poor progression-free survival and OS in small-cell lung cancer patients after first-line chemo-therapy.…”

The Effect of Mitomycin C on Reducing Endometrial Fibrosis for Intrauterine Adhesion

“…IUA is mainly caused by damage to the basal layer of endometrium [2]. IUA is most common in trauma or infection, especially when the level of estradiol is low after pregnancy [3]. During the healing process, the opposing walls of the uterus adhere together, causing occlusion of the uterine cavity [4,5].…”