Department of Obstetrics & Gynecology, Tufts University School of Medicine, Boston, USA.
Mother Infant Research Institute, Tufts Medical Center, Boston, USA.
Reprod Sci. 2020 Jul;27(7):1383-1390. doi: 10.1007/s43032-020-00164-z. Epub 2020 Feb 19.
Iron is an essential element for cell survival, and iron deficiency is a known risk factor for many reproductive disorders. Paradoxically, such disorders are also seen more commonly under conditions of iron excess. Here, we focus on the problem of iron overload in women's health, using endometriosis as a model system. We propose (i) that a primary defect in endometriosis is abnormal eutopic endometrium characterized by resistance to ferroptosis, a process of iron-mediated non-apoptotic programmed cell death, which allows cells spread via retrograde menstruation to survive, implant, and establish endometriotic lesions within the abdominal cavity, and (ii) that dysregulated iron homeostasis may be critical to the subsequent pathophysiology of endometriotic lesions with localized iron overload and inflammation. We further investigate the association between endometriosis and hypercholesterolemia and suggest that an interaction between the mevalonate cholesterol biosynthetic pathway and ferroptosis signaling may provide a molecular basis to explain how it is that, in some women, endometrial tissues survive and thrive under ferroptotic pressure, colonize at ectopic sites, and expand into endometriotic lesions.
铁是细胞生存所必需的元素，铁缺乏是许多生殖障碍的已知危险因素。矛盾的是，在铁过量的情况下，这种障碍也更为常见。在这里，我们以子宫内膜异位症为模型系统，关注女性健康中的铁过载问题。我们提出：（i）子宫内膜异位症的一个主要缺陷是异常的在位子宫内膜，其特征是对铁死亡的抗性，铁死亡是一种铁介导的非凋亡程序性细胞死亡过程，使细胞通过逆行月经扩散得以存活、植入并在腹腔内建立子宫内膜异位病灶；（ii）铁稳态失调可能对子宫内膜异位病灶的后续病理生理学具有关键作用，导致局部铁过载和炎症。我们进一步研究了子宫内膜异位症与高胆固醇血症之间的关系，并提出甲羟戊酸胆固醇生物合成途径和铁死亡信号之间的相互作用可能为解释为什么在某些女性中，子宫内膜组织在铁死亡压力下得以存活和生长、在异位部位定植以及扩张为子宫内膜异位病灶提供了分子基础。
