子宫内膜异位症是一种以氧化应激和慢性炎症增加为特征的疾病，可以用孕激素和其他孕激素受体配体来治疗。然而，一些患者对此治疗无效，原因尚不明确。本研究旨在调查选择性孕激素受体调节剂烯孕酮乙酸酯（UPA）对经组织学确诊的子宫内膜异位症患者（n = 22）和无子宫内膜异位症患者（n = 6）的子宫内膜细胞和间质细胞增殖、产生活性氧（ROS）和促炎细胞因子的影响。上皮细胞和间质细胞被分离并连续24小时接受1 μM、10 μM或100 μM UPA的处理。检测细胞增殖和ROS产生，同时对细胞上清液进行检测，测定白细胞介素（IL）-6、C-C基序趋化因子配体2（CCL2）和肿瘤坏死因子（TNF）-α浓度。与子宫内膜异位症患者和对照组相比，未刺激的子宫内膜异位症病灶上皮和间质细胞的增殖、ROS产生、IL-6和CCL2分泌增加。UPA仅在子宫内膜异位症中量依赖性增加细胞增殖，同时增强了所有细胞类型的ROS产生。UPA降低了对照组的CCL2产生，但在子宫内膜异位症中未实现，而TNF-α不可测量。我们得出结论，在治疗子宫内膜异位症时，UPA对细胞的处理刺激了体外增殖和ROS产生，并未逆转这些细胞所特征的过多的促炎细胞因子产生，揭示了药物耐药的可能机制。© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.

Endometriosis is a condition characterized by increased oxidative stress and chronic inflammation, which can be treated with progestins and other progesterone receptor ligands. However, some patients are refractory to this treatment and the reason is uncertain. Here we investigated the effects of the selective progesterone receptor modulator ulipristal acetate (UPA) on proliferation, reactive oxygen species (ROS), and proinflammatory cytokine production by endometriotic cells and endometrial cells from women with histologically proven endometriosis (n = 22) and endometriosis-free controls (n = 6). Epithelial and stromal cells were isolated and treated in triplicate for 24 h with 1 μM, 10 μM, or 100 μM UPA. Cells were tested for proliferation and ROS production, while cell supernatants were assayed for interleukin (IL)-6, C-C motif chemokine ligand 2 (CCL2), and tumor necrosis factor (TNF)-α concentrations. Proliferation, ROS production, and IL-6 and CCL2 secretion were increased in non-stimulated epithelial and stromal cells from endometriotic lesions compared to endometrial cells from endometriosis patients and controls. UPA induced a dose-dependent increase of cell proliferation only in endometriosis, while enhancing ROS production by all cell types evaluated. UPA reduced CCL2 production in controls but failed to do that in endometriosis, whereas TNF-α was undetectable. We conclude that treatment of endometriotic cells with UPA stimulated in vitro proliferation and ROS production and failed to revert the proinflammatory cytokine excess that characterized these cells, unravelling possible mechanisms of drug resistance in the treatment of endometriosis.© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.