Gynecology Department, The Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China.
Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai 200011, China.
Int J Mol Sci. 2023 Dec 19;25(1):29. doi: 10.3390/ijms25010029.
Studies have shown that the occurrence and development of endometriosis are closely linked to long-term psychological stress. The specific contribution of chronic stress to the metabolic adaptations in patients with endometriosis is still unknown. Lesions were removed from ten endometriosis patients during an operation, and the participants were divided into two groups using a psychological questionnaire. An mRNA Human Gene Expression Microarray analysis was applied to compare the mRNA expression profiles between the chronic stress group and the control group. In addition, the reliability of the mRNA Human Gene Expression Microarray analysis was verified by using research on metabolites based on both the liquid chromatography (LC-MS/MS) technique and quantitative reverse transcription polymerase chain reaction (RT-PCR). A microarray analysis of significantly up-regulated, differentially expressed genes between the chronic stress and the control groups showed genes that were principally related to metabolism-related processes and immune-related processes, such as the immune response process, negative regulation of T cell proliferation, the leucine metabolic process, and the L-cysteine metabolic process ( < 0.05). LC-MS showed that the differential metabolites were primarily concerned with arginine and proline metabolism, D-glutamine and D-glutamate metabolism, aspartate metabolism, glycine, serine metabolism, and tyrosine metabolism ( < 0.05). The possibility of chronic stress blocks the endometriosis immune response through metabolic reprogramming. Chronic stress reduces the supply of energy substrates such as arginine and serine, down-regulates T immune cell activation, and affects the anti-tumor immune response, thereby promoting the migration and invasion of endometriosis lesions in patients with chronic stress.
研究表明,子宫内膜异位症的发生和发展与长期的心理压力密切相关。慢性应激对子宫内膜异位症患者代谢适应的具体贡献尚不清楚。在手术过程中从 10 名子宫内膜异位症患者身上切除病变组织,并使用心理问卷将参与者分为两组。应用 mRNA 人类基因表达微阵列分析比较慢性应激组和对照组之间的 mRNA 表达谱。此外,还使用基于液相色谱(LC-MS/MS)技术和定量逆转录聚合酶链反应(RT-PCR)的代谢物研究验证了 mRNA 人类基因表达微阵列分析的可靠性。慢性应激组和对照组之间差异表达基因的微阵列分析显示,主要与代谢相关过程和免疫相关过程相关的基因上调,如免疫反应过程、T 细胞增殖的负调控、亮氨酸代谢过程和 L-半胱氨酸代谢过程(<0.05)。LC-MS 显示差异代谢物主要与精氨酸和脯氨酸代谢、D-谷氨酰胺和 D-谷氨酸代谢、天冬氨酸代谢、甘氨酸、丝氨酸代谢和酪氨酸代谢有关(<0.05)。慢性应激可能通过代谢重编程阻断子宫内膜异位症的免疫反应。慢性应激会减少精氨酸和丝氨酸等能量底物的供应,下调 T 免疫细胞的激活,影响抗肿瘤免疫反应,从而促进慢性应激患者子宫内膜异位症病变的迁移和侵袭。