SCGB1D4 Downregulation Links to Fibrosis in Intrauterine Adhesion Patients and Rat Models.

Abstract

Background: Intrauterine adhesions (IUA) represent a prevalent uterine endometrial disorder frequently correlated with menstrual irregularities and infertility. This study aims to examine the expression of SCGB1D4 in IUA tissues and assess its potential therapeutic implications by analyzing clinical features and constructing rat and cell models.

Methods: Clinical characteristics of patients with intrauterine adhesions were compared and analyzed against control subjects. Additionally, a rat uterine adhesion model was successfully established using a combination of mechanical injury and infection. The expression levels of SCGB1D4 in patient tissues and animal models were detected through immunohistochemistry, Western blot, and real-time fluorescence quantitative PCR, and the changes in fibrosis markers COL1A1 and α-SMA were also evaluated. Furthermore, human endometrial stromal cell lines (HESCs) induced by transforming growth factor-β-1 conversion were differentiated into myofibroblasts to establish cell models of intrauterine adhesion. We detected the expression of SCGB1D4 and fibrosis-related factors by real-time fluorescence quantitative PCR and Western blot. Cell proliferation and cell cycle changes were assessed using flow cytometry and CCK8.

Results: IUA patients showed increased miscarriage rates and decreased endometrial thickness. Clinical tissue specimens revealed significantly lower expression of SCGB1D4 in the endometrial tissues of IUA patients, accompanied by a notable increase in COL1A1 and α-SMA. The established rat model of intrauterine adhesion exhibited decreased expression of SCGB1D4 and a significant increase in fibrosis. After overexpression of SCGB1D4 on the IUA cell model, SCGB1D4 expression was elevated, while COL1A1 and α-SMA expression was significantly reduced. Cell proliferation was inhibited and cell cycle distribution was altered.

Conclusions: This study has confirmed the low expression of SCGB1D4 in patients with intrauterine adhesions (IUA), as well as in animal and cell models. Furthermore, the overexpression of SCGB1D4 in a cell model of IUA demonstrates that it may play a key role in inhibiting fibrosis. SCGB1D4 holds promise as a potential therapeutic target for IUA, providing a new avenue for overcoming fertility issues caused by intrauterine adhesions.