Department of Obstetrics & Gynaecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
Reprod Sci. 2013 Sep;20(9):1020-9. doi: 10.1177/1933719113477483. Epub 2013 Mar 1.
Preeclampsia (PE) remains a major cause of maternal/fetal morbidity-mortality worldwide. The first stage of PE is characterized by placental hypoxia due to a relative reduction in uteroplacental blood flow, resulting from restricted trophoblast invasion. However, hypoxia is also an essential element for the success of invasion. Under hypoxic conditions, 2-methoxyestradiol (2-ME) could induce the differentiation of cytotrophoblast cells into an invasive phenotype in culture. 2-Methoxyestradiol is generated by catechol-O-methyltransferase, an enzyme involved in the metabolic pathway of estrogens. During pregnancy, circulating 2-ME levels increase significantly when compared to the menstrual cycle. Interestingly, plasma levels of 2-ME are lower in women with PE than in controls, and these differences are apparent weeks or even months before the clinical manifestations of the disease. This article reviews the metabolic pathways involved in 2-ME synthesis and discusses the roles of these pathways in normal and abnormal pregnancies, with particular emphasis on PE.
子痫前期 (PE) 仍然是全球孕产妇/胎儿发病率和死亡率的主要原因。PE 的第一阶段的特征是胎盘缺氧，这是由于胎盘血流相对减少所致，而胎盘血流减少是由于滋养细胞侵袭受限。然而，缺氧也是侵袭成功的必要因素。在缺氧条件下，2-甲氧基雌二醇 (2-ME) 可诱导滋养细胞向侵袭表型分化。2-ME 是由儿茶酚-O-甲基转移酶生成的，儿茶酚-O-甲基转移酶是雌激素代谢途径中的一种酶。在怀孕期间，与月经周期相比，循环中的 2-ME 水平显著增加。有趣的是，与对照组相比，PE 患者的血浆 2-ME 水平较低，而且这些差异在疾病的临床表现出现前数周甚至数月就已经明显。本文综述了 2-ME 合成涉及的代谢途径，并讨论了这些途径在正常和异常妊娠中的作用，特别强调了 PE。
