Metabolic pathways involved in 2-methoxyestradiol synthesis and their role in preeclampsia

Alejandra Perez-Sepulveda, Pedro P. España-Perrot, Errol R. Norwitz, Sebastián E. Illanes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish
Pages (from-to)1020-1029
Number of pages10
JournalReproductive Sciences
Issue number9
StatePublished - Sep 2013

Bibliographical note

© The Author(s) 2013.


  • 2-methoxyestradiol (2-ME)
  • aromatase
  • hypoxia
  • methionine-homocysteine metabolism
  • preeclampsia


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