Fan Weisen, Zhang Yingjie, Dai Yuanquan, Ma Haotian, Zhao Ruihua, Liu Yong
Department of Gynecology, Guang 'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250013, China.
Exp Cell Res. 2025 May 1;448(1):114553. doi: 10.1016/j.yexcr.2025.114553. Epub 2025 Apr 9.
Ovarian endometriosis(OEM) is the most common type of endometriosis, but there is still a lack of simple and easy-to-promote animal models. Therefore, it is necessary to establish a feasible animal model of OEM and analyze its pathogenesis. In this study, a novel insertional surgical method was used to construct the OEM rat model. The rat model group's morphology and HE staining revealed a close relationship between the transplanted ectopic tissue and the ovary. Compared to the surgery group and the normal group, the bilateral OEM group's level of Anti-mullerian hormone(AMH) was noticeably lower. There was no discernible difference in the unilateral OEM group's AMH level between the normal and sham operation groups. Serum interleukin-1beta(IL-1β) levels in four groups of rats showed bilateral OEM had the greatest level, followed by unilateral OEM. Compared to the normal group, the two model groups had greater serum levels of IL-1β. According to immunohistochemistry, unilateral OEM had higher Intercellular adhesion molecule 1(ICAM1), Matrix metalloproteinase-9(MMP9), Tumor necrosis factor-α(TNF-a), and IL-1β expression levels than the normal rat endometrium. WB revealed that bilateral and unilateral ectopic tissues had higher levels of MMP9, TNF-a, Vascular endothelial growth factor D and IL-1β expression than normal tissues. Transcriptome research revealed that ectopic tissues had higher pro-inflammatory, immunological, and ectopic endometrial proliferation pathways than normal tissues. The ovaries of unilateral OEM have down-regulated immune and inflammation-related pathways and up-regulated steroid hormones compared to normal ovarian tissue. GSEA enrichment analysis comparisons between rat and human endometriotic tissue revealed that Janus kinase-signal transducer and activator of transcription(JAK-STAT), Nuclear factor-kappa B(NFκB), and Toll-like receptors were up-regulated. The intercalation approach of OEM building used in this work is more akin to the human OEM lesion type. It deserves promotion that modeling is more straightforward and has a higher success rate than the suture approach.
卵巢子宫内膜异位症（OEM）是最常见的子宫内膜异位症类型，但仍缺乏简单且易于推广的动物模型。因此，有必要建立一种可行的OEM动物模型并分析其发病机制。在本研究中，采用了一种新型的植入手术方法构建OEM大鼠模型。大鼠模型组的形态学和苏木精-伊红（HE）染色显示移植的异位组织与卵巢之间存在密切关系。与手术组和正常组相比，双侧OEM组的抗苗勒管激素（AMH）水平明显较低。单侧OEM组的AMH水平在正常组和假手术组之间没有明显差异。四组大鼠的血清白细胞介素-1β（IL-1β）水平显示，双侧OEM组最高，其次是单侧OEM组。与正常组相比，两个模型组的血清IL-1β水平更高。免疫组织化学显示，单侧OEM的细胞间黏附分子1（ICAM1）、基质金属蛋白酶-9（MMP9）、肿瘤坏死因子-α（TNF-α）和IL-1β表达水平高于正常大鼠子宫内膜。蛋白质免疫印迹法（WB）显示，双侧和单侧异位组织中MMP9、TNF-α、血管内皮生长因子D和IL-1β的表达水平高于正常组织。转录组研究表明，异位组织的促炎、免疫和异位子宫内膜增殖途径高于正常组织。与正常卵巢组织相比，单侧OEM的卵巢免疫和炎症相关途径下调，类固醇激素上调。大鼠和人类子宫内膜异位组织之间的基因集富集分析（GSEA）比较显示，Janus激酶-信号转导子和转录激活子（JAK-STAT）、核因子-κB（NFκB）和Toll样受体上调。本研究中使用的OEM构建插入方法更类似于人类OEM病变类型。其建模更简单，成功率高于缝合方法，值得推广。
