铁死亡是胞质内铁稳态失衡触发胞内脂质过氧化导致的程序性细胞死亡。出血是引发铁失衡、驱动铁死亡的重要原因。内异症腹腔及病灶微环境分别因周期性经血逆流和出血而存在铁蓄积过载的失衡状态。我们的前期研究发现，模拟腹腔液铁离子浓度培养的正常子宫内膜间质细胞（ESC）发生铁死亡；而异位内膜ESC异乎寻常地并未发生铁死亡。其胞质内铁的转运与贮存可能发生了某种适应性改变从而维护了胞质铁稳态阈值。由此我们提出“异位内膜通过NCOA4-VDACs/FtMt转铁途径维稳胞内铁离子水平，免于启动铁死亡程序而获得生存”的构想。本研究拟行体外及体内实验，通过干预NCOA4-VDACs/FtMt表达，解析不同铁浓度下ESC胞质和贮铁细胞器中铁离子的分布格局、氧化与抗氧化能力、铁死亡基因等变化；借助内异症小鼠模型验证诱导铁死亡对內异灶形成的影响。籍此揭示异位内膜耐受铁死亡的分子机制，探寻内异症非激素治疗的途径或靶点。

Ferroptosis is a programmed cell deathcaused by the accumulation of ferrous ions in the cytoplasm, which can catalyze lipid into a variety of reactive oxygen species (ROS) even exceed the compensatory of the antioxidant system, resulting in DNA damage and modification as well as cell death finally. Bleeding is an important cause of iron imbalance and ferroptosis. Endometriosis involves the theory of menstrual blood reflux, and lesions show the characteristic of periodic bleeding along with hormone level changes, all which will improve the iron accumulation and format the pathological environment specialized with high level iron concentration in the abdominal cavity. Our previous study found that, in the culture medium simulated peritoneal fluid iron concentration, the normal endometrial stromal cells (ESCs) appeared ferroptosis while the ectopic ESCs did not. These results suggested that the transport and storage of intracellular iron may have undergone some adaptive changes to maintain the cytoplasmic iron homeostasis threshold.Thus we put forward that "NCOA4-VDACs/FtMtpathway can improve the viability of ectopic endometrial cells in the cruel environment via changing the iron metabolism and further inhibit subsequent ferroptosis". This study proposed by in vivo and in vitro experiments, through intervention the expressionof NCOA4-VDACs/FtMt, aims to explore the distribution pattern of iron, the oxidation level, the capacity of antioxidant as well as the changes of gene expression in ESCs cultured in different iron concentration medium.The impact of ferroptosis on the formation of endometrial lesions was verified by endometriosis mouse model. We expect this research can not only reveals the molecular mechanism of ferroptosis tolerance but also provide a hormone-independent therapeutic targets in endometriosis in the future.