Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research Polish Academy of Sciences in Olsztyn, Olsztyn, Poland.
Center for Experimental and Innovative Medicine, University of Agriculture in Cracow, Cracow, Poland.
Sci Rep. 2023 Sep 27;13(1):16263. doi: 10.1038/s41598-023-43359-5.
In the current study, transcriptome profiles of mare endometrium, classified into categories I, IIA, and IIB according to Kenney and Doig, were compared using RNA sequencing, analyzed, and functionally annotated using in silico analysis. In the mild stage (IIA) of endometrosis compared to category I endometrium, differentially expressed genes (DEGs) were annotated to inflammation, abnormal metabolism, wound healing, and quantity of connective tissue. In the moderate stage (IIB) of endometrosis compared to category I endometrium, DEGs were annotated to inflammation, fibrosis, cellular homeostasis, mitochondrial dysfunction, and pregnancy disorders. Ingenuity pathway analysis (IPA) identified cytokines such as transforming growth factor (TGF)-β1, interleukin (IL)-4, IL-13, and IL-17 as upstream regulators of DEGs associated with cellular homeostasis, metabolism, and fibrosis signaling pathways. In vitro studies showed the effect of these cytokines on DEGs such as ADAMTS1, -4, -5, -9, and HK2 in endometrial fibroblasts at different stages of endometrosis. The effect of cytokines on ADAMTS members' gene transcription in fibroblasts differs according to the severity of endometrosis. The identified transcriptomic changes associated with endometrosis suggest that inflammation and metabolic changes are features of mild and moderate stages of endometrosis. The changes of ADAMTS-1, -4, -5, -9, in fibrotic endometrium as well as in endometrial fibroblast in response to TGF-β1, IL-4, IL-13, and IL-17 suggest the important role of these factors in the development of endometrosis.
在当前的研究中,根据 Kenney 和 Doig 的分类,将马子宫内膜分为 I 型、IIA 型和 IIB 型,并使用 RNA 测序进行比较,通过计算机分析进行分析和功能注释。与 I 型子宫内膜相比,在子宫内膜异位症的轻度阶段(IIA),差异表达基因(DEG)被注释为炎症、代谢异常、伤口愈合和结缔组织数量。与 I 型子宫内膜相比,在子宫内膜异位症的中度阶段(IIB),DEG 被注释为炎症、纤维化、细胞内稳态、线粒体功能障碍和妊娠障碍。Ingenuity 通路分析(IPA)确定了转化生长因子 (TGF)-β1、白细胞介素 (IL)-4、IL-13 和 IL-17 等细胞因子作为与细胞内稳态、代谢和纤维化信号通路相关的 DEG 的上游调节剂。体外研究表明,这些细胞因子在子宫内膜异位症不同阶段的子宫内膜成纤维细胞中对 DEG 如 ADAMTS1、-4、-5、-9 和 HK2 的作用。细胞因子对成纤维细胞中 ADAMTS 成员基因转录的影响因子宫内膜异位症的严重程度而异。与子宫内膜异位症相关的转录组变化表明,炎症和代谢变化是轻度和中度子宫内膜异位症的特征。ADAMTS-1、-4、-5、-9 在纤维化子宫内膜以及对 TGF-β1、IL-4、IL-13 和 IL-17 反应的子宫内膜成纤维细胞中的变化表明这些因素在子宫内膜异位症的发展中具有重要作用。