Zhao Jing, Wang Yuanhui, Ma Chanchan, Feng Yifan, Wang Yunmeng, Sun Shiying
Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, P. R. China.
Biol Reprod. 2025 Feb 14;112(2):273-285. doi: 10.1093/biolre/ioae172.
Intrauterine adhesions (IUA) represent a prevalent uterine endometrial disorder frequently correlated with menstrual irregularities and infertility. Some members of the secretoglobin(SCGB) family have demonstrated anti-fibrotic effects, however, the specific role of SCGB1D4, one of the family members, in anti-fibrosis remains unclear. This study aimed to investigate the expression of SCGB1D4 in IUA tissues, validate the role of SCGB1D4 in endometrial fibrosis, and assess its potential therapeutic significance by analyzing clinical features and constructing rat and cell models. Clinical characteristics of patients with intrauterine adhesions (IUA) 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. 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. This study has confirmed the low expression of SCGB1D4 in patients with 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 IUA.
宫腔粘连（IUA）是一种常见的子宫内膜疾病，常与月经不调和不孕相关。分泌球蛋白（SCGB）家族的一些成员已显示出抗纤维化作用，然而，该家族成员之一SCGB1D4在抗纤维化中的具体作用仍不清楚。本研究旨在探讨SCGB1D4在IUA组织中的表达，验证SCGB1D4在子宫内膜纤维化中的作用，并通过分析临床特征以及构建大鼠和细胞模型来评估其潜在的治疗意义。将宫腔粘连（IUA）患者的临床特征与对照受试者进行比较和分析。此外，采用机械损伤和感染相结合的方法成功建立了大鼠子宫粘连模型。通过免疫组织化学、蛋白质免疫印迹和实时荧光定量PCR检测患者组织和动物模型中SCGB1D4的表达水平，并评估纤维化标志物COL1A1和α-SMA的变化。此外，将转化生长因子-β-1转化诱导的人子宫内膜基质细胞系（HESCs）分化为肌成纤维细胞，建立宫腔粘连细胞模型。通过实时荧光定量PCR和蛋白质免疫印迹检测SCGB1D4和纤维化相关因子的表达。使用流式细胞术和CCK8评估细胞增殖和细胞周期变化。IUA患者流产率增加，子宫内膜厚度降低。临床组织标本显示，IUA患者子宫内膜组织中SCGB1D4表达明显降低，同时COL1A1和α-SMA显著增加。建立的大鼠宫腔粘连模型显示SCGB1D4表达降低，纤维化显著增加。在IUA细胞模型上过表达SCGB1D4后，SCGB1D4表达升高，而COL1A1和α-SMA表达显著降低。细胞增殖受到抑制，细胞周期分布发生改变。本研究证实了SCGB1D4在IUA患者以及动物和细胞模型中的低表达。此外，在IUA细胞模型中过表达SCGB1D4表明它可能在抑制纤维化中起关键作用。SCGB1D4有望成为IUA的潜在治疗靶点，为克服IUA引起的生育问题提供新途径。
