Endometriosis-associated ovarian carcinogenesis induced by iron-dependent oxidative stress

本研究的目的是描述基因组的不稳定性、遗传多态及其单倍型、与子宫内膜异位症易感性相关的表观遗传学改变，以及与子宫内膜异位症相关的卵巢肿瘤相关的关键因素。逆行月经导致铁超载，从而通过芬顿反应介导的氧化应激促进体细胞突变的积累。子宫内膜异位症的发展似乎至少有三个不同的时空阶段：从父母那里遗传的遗传背景的初始阶段，紧随其后的是雌性后代的第二大表观遗传修饰阶段，以及铁超载的最后阶段，这一阶段在以后的生活中受到动态调节。子宫内膜异位症易感基因的戏剧性调节可能来自于基于微环境变化的表观遗传和遗传突变的机制。

The aim of the present study is to describe genomic instability, genetic polymorphisms and their haplotype, epigenetic alterations associated with endometriosis predisposition, and the key factors that have been linked to endometriosis-related ovarian neoplasms. Retrograde menstruation leads to iron overload, which facilitates the accumulation of somatic mutations through a Fenton reaction-mediated oxidative stress. There seems to be at least three spatiotemporally distinct phases of endometriosis development: The initial phase of genetic background inherited from parents would be followed by the second big wave of epigenetic modifications in the female offspring and the final phase of the iron overload that is subject to dynamic modulation later in life. The dramatic regulation of endometriosis susceptibility genes may come from a mechanism responsible for epigenetic and genetic mutations based on the microenvironmental changes.