The TNF-α/TNFR system is involved in endometriosis (EDT), a gynecologic estrogen-dependent disease. Elevated copper concentrations have also been associated with EDT, even in TNFR1-deficient mice where disease worsening occurs. We aimed to evaluate whether treatment with ammonium tetrathiomolybdate (TM, copper chelator) is beneficial in TNFR1-deficient mice presenting with worsened EDT status. Female C57BL/6 mice were divided into three groups: KO Sham, KO EDT, and KO EDT+TM. TM was administered from the 15th postoperative day, and samples were collected one month after inducing pathology. In peritoneal fluid, copper and estradiol levels were determined by electrothermal atomic absorption spectrometry and electrochemiluminescence, respectively. Lesions were processed for the analysis of cell proliferation (PCNA immunohistochemistry), expression of angiogenic markers (RT-qPCR), and oxidative stress (spectrophotometric methods). We found that EDT increased copper and estradiol levels compared to the KO Sham group, while the TM administration restored the levels of both factors. TM also reduced the volume and weight of the lesions and cell proliferation rate. Besides, TM treatment decreased the number of blood vessels and the Vegfa, Fgf2, and Pdgfb expression. Furthermore, superoxide dismutase and catalase activity decreased, and lipid peroxidation increased. TM administration inhibits EDT progression in TNFR1-deficient mice where the pathology is exacerbated.

TNF-α/TNFR 系统与子宫内膜异位症（EDT）有关，这是一种妇科雌激素依赖性疾病。铜浓度升高也与 EDT 有关，即使是在 TNFR1 缺陷的小鼠中，疾病也会恶化。我们的目的是评估四硫代钼酸铵（TM，铜螯合剂）治疗对于 EDT 状态恶化的 TNFR1 缺陷小鼠是否有益。雌性 C57BL/6 小鼠分为三组：KO Sham、KO EDT 和 KO EDT+TM。术后第15天开始注射TM，诱导病理后1个月采集样本。腹膜液中铜和雌二醇的水平分别通过电热原子吸收光谱法和电化学发光法测定。对病变进行处理以分析细胞增殖（PCNA 免疫组织化学），血管生成标记物的表达（RT-qPCR）和氧化应激（分光光度法）。我们发现，与 KO Sham 组相比，EDT 增加了铜和雌二醇水平，而 TM 给药则恢复了这两个因子的水平。TM还降低了病变的体积和重量以及细胞增殖率。此外，TM治疗减少了血管数量和Vegfa、Fgf2和Pdgfb表达。此外，超氧化物歧化酶和过氧化氢酶活性降低，脂质过氧化增加。TM 给药可抑制 TNFR1 缺陷小鼠的 EDT 进展，从而使病理恶化。