Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Endocrinol (Lausanne). 2022 Oct 20;13:945578. doi: 10.3389/fendo.2022.945578. eCollection 2022.
Endometriosis (EMS) is a chronic gynecological disease that affects women of childbearing age. However, the exact cause remains unclear. The uterus is a highly vascularized organ that continuously exposes endometrial cells to high oxygen concentrations. According to the "planting theory" of EMS pathogenesis, when endometrial cells fall from the uterine cavity and retrograde to the peritoneal cavity, they will face severe hypoxic stress. Hypoxic stress remains a key issue even if successfully implanted into the ovaries or peritoneum. In recent years, increasing evidence has confirmed that hypoxia is closely related to the occurrence and development of EMS. Hypoxia-inducible factor-1α (HIF-1α) can play an essential role in the pathological process of EMS by regulating carbohydrate metabolism, angiogenesis, and energy conversion of ectopic endometrial cells. However, HIF-1α alone is insufficient to achieve the complete program of adaptive changes required for cell survival under hypoxic stress, while the unfolded protein response (UPR) responding to endoplasmic reticulum stress plays an essential supplementary role in promoting cell survival. The formation of a complex signal regulation network by hypoxia-driven UPR may be the cytoprotective adaptation mechanism of ectopic endometrial cells in unfavorable microenvironments.
子宫内膜异位症（EMS）是一种影响育龄妇女的慢性妇科疾病。然而，确切的病因仍不清楚。子宫是一个高度血管化的器官，子宫内膜细胞持续暴露在高氧浓度下。根据 EMS 发病机制的“种植理论”，当子宫内膜细胞从子宫腔脱落并逆行到腹腔时，它们将面临严重的缺氧应激。即使成功植入卵巢或腹膜，缺氧应激仍然是一个关键问题。近年来，越来越多的证据证实，缺氧与 EMS 的发生和发展密切相关。缺氧诱导因子-1α（HIF-1α）可通过调节异位子宫内膜细胞的糖代谢、血管生成和能量转换，在 EMS 的病理过程中发挥重要作用。然而，HIF-1α 本身不足以实现细胞在缺氧应激下生存所需的完整适应变化程序，而内质网应激反应的未折叠蛋白反应（UPR）则在促进细胞生存方面发挥着重要的补充作用。由缺氧驱动的 UPR 形成的复杂信号调节网络可能是异位子宫内膜细胞在不利微环境中细胞保护适应机制。
