Abnormal expression of fibrosis markers, estrogen receptor α and stromal derived factor-1/chemokine (C-X-C motif) receptor-4 axis in intrauterine adhesions

Abstract

Intrauterine adhesions (IUAs) are mainly derived from fibrous tissue formation following endometrial damage. The aim of the present study was to assess whether fibrosis markers, estrogen receptor (ER)α and the stromal derived factor (SDF)-1/C-X-C chemokine receptor type 4 (CXCR-4) axis are abnormally expressed in IUA endometrium. A total of 76 human endometrial biopsy samples (normal, n=20; mild-to-moderate IUAs, n=40; and severe IUAs, n=16) were employed, and Sprague-Dawley rat IUA models at different time points were constructed. Subsequently, the expression of transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-9, ERα and the SDF-1/CXCR-4 axis was evaluated in human and rat IUAs using histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction and western blotting. In patients and rats with IUA formation, the expression of TGF-β1, MMP-9 and ERα was significantly higher compared with the control group at the mRNA and protein levels (P<0.05); in addition, in patients, the TGF-β1, MMP-9 and ERα levels were significantly higher in severe IUAs compared with those in mild-to-moderate IUA endometrium (P<0.05). Although the chemokine SDF-1 level in rats increased significantly during the early postoperative phase (reaching a peak at the second estrus phase) in rat endometrium (P<0.05), its special receptor CXCR-4 expression did not differ significantly compared with the control group in rats or patients (P>0.05). Our findings indicated that aberrant activation of fibrosis and expression of ERα may be involved in the pathology of IUA formation. The role of the SDF-1/CXCR-4 axis in IUAs as inflammatory medium in the short-term or special homing factors for bone marrow mesenchymal stem cells requires further verification in in vivo animal models.