Zhu Jing, Li Zhenyao, Yin Fengli, Yu Xiaoting, Lu Yuanfan, Zhou Tong, Gong Fanghua, Xu Zhangye
Department of Gynecology and Obstetrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
Front Pharmacol. 2023 Apr 20;14:1143096. doi: 10.3389/fphar.2023.1143096. eCollection 2023.
: Thin endometrium is a reproductive disorder that affects embryo implantation. There are several therapies available for this disease, however they are not so effective. Fibroblast growth factor 1 (FGF1) is a member of fibroblast growth factor superfamily (FGFs), and it has been demonstrated that FGF1 expression was altered in samples collected from patients with thin endometrium. However, it is unclear if FGF1 could improve thin endometrium. The aim of this study was to investigate whether FGF1 have a therapeutic effect on thin endometrium. A model of thin endometrium induced by ethanol was constructed to investigate the effect and mechanism of action of FGF1 in thin endometrium. In the characterization experiments, 6-8 weeks female rats (n = 40) were divided into four groups: i) Control group; ii) Sham group; iii) Injured group; (iv) FGF1 therapy group. Endometrial tissues would be removed after three sexuel cycles after molding. Morphology and histology of the endometrium were evaluated by visual and hematoxylin and eosin staining. Masson staining and expression of α-SMA in endometrium showed the degree of endometrial fibrosis. Western blotting (PCNA、vWF and Vim) and immunohistochemistry (CK19 and MUC-1) demonstrated the effect of FGF1 on cell proliferation and angiogenesis. Moreover, immunohistochemistry (ER and PR) was used to explore the function of endometrium. The remaining rats (n = 36) were divided into three groups: i) Injured group; ii) FGF1 therapy group; and iii) 3-methyladenine. Western blotting (p38、p-p38、PI3K 、SQSTM1/p62、beclin-1 and LC3) was used to explore the mechanisms of FGF1. In FGF1 therapy group, the morphology and histology of endometrium improved compared with the model group. Masson staining and the expression level of α-SMA showed that FGF1 could decrease the fibrotic area of endometrium. Besides, changes in ER and PR expression in the endometrium suggested that FGF1 could restore endometrium-related functions. Western blotting and immunohistochemistry revealed that PCNA, vWF, Vim, CK19 and MUC-1 were significantly increased after FGF1 treatment compared with the thin endometrium. In addition, Western blotting showed that p38, p-p38, PI3K, SQSTM1/p62, beclin-1 and LC3 levels were higher in FGF1 group than in the injured group. FGF1 application cured the thin endometrium caused by ethanol through autophagy mechanism.
薄型子宫内膜是一种影响胚胎着床的生殖系统疾病。针对该疾病有多种治疗方法，但效果都不太理想。成纤维细胞生长因子1（FGF1）是成纤维细胞生长因子超家族（FGFs）的成员之一，已有研究表明，从薄型子宫内膜患者采集的样本中FGF1表达发生了改变。然而，FGF1是否能改善薄型子宫内膜尚不清楚。本研究旨在探讨FGF1对薄型子宫内膜是否具有治疗作用。构建了乙醇诱导的薄型子宫内膜模型，以研究FGF1在薄型子宫内膜中的作用效果及作用机制。在特性实验中，将6 - 8周龄雌性大鼠（n = 40）分为四组：i）对照组；ii）假手术组；iii）损伤组；（iv）FGF1治疗组。造模后经过三个性周期后取出子宫内膜组织。通过肉眼观察以及苏木精 - 伊红染色评估子宫内膜的形态和组织学变化。Masson染色以及子宫内膜中α - SMA的表达显示子宫内膜纤维化程度。蛋白质免疫印迹法（检测PCNA、vWF和Vim）和免疫组织化学法（检测CK19和MUC - 1）证明FGF1对细胞增殖和血管生成的影响。此外，免疫组织化学法（检测ER和PR）用于探究子宫内膜的功能。其余大鼠（n = 36）分为三组：i）损伤组；ii）FGF1治疗组；iii）3 - 甲基腺嘌呤组。采用蛋白质免疫印迹法（检测p38、p - p38、PI3K、SQSTM1/p62、beclin - 1和LC3）探究FGF1的作用机制。在FGF1治疗组中，与模型组相比，子宫内膜的形态和组织学得到改善。Masson染色以及α - SMA的表达水平表明FGF1可减少子宫内膜的纤维化面积。此外，子宫内膜中ER和PR表达的变化表明FGF1可恢复子宫内膜相关功能。蛋白质免疫印迹法和免疫组织化学法显示，与薄型子宫内膜组相比，FGF1治疗后PCNA、vWF、Vim、CK19和MUC - 1显著增加。此外，蛋白质免疫印迹法显示，FGF1组中p38、p - p38、PI3K、SQSTM1/p62、beclin - 1和LC3水平高于损伤组。FGF1通过自噬机制治愈了乙醇所致的薄型子宫内膜。
