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Metabolic Pathways Involved in 2-Methoxyestradiol Synthesis and Their Role in Preeclampsia

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Abstract

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.

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Authors and Affiliations

  1. Department of Obstetrics & Gynaecology and Laboratory of Reproductive Biology, Faculty of Medicine, Universidad de Los Andes, Santiago, 7620001, Chile

    Alejandra Perez-Sepulveda PhD, Pedro P. España-Perrot BSc & Sebastián E. Illanes MS, MD

  2. Mother Infant Research Institute and Department of Obstetrics & Gynecology, Tufts University School of Medicine, Boston, MA, USA

    Errol R. Norwitz MD, PhD

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  1. Alejandra Perez-Sepulveda PhD
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Correspondence to Sebastián E. Illanes MS, MD.

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Perez-Sepulveda, A., España-Perrot, P.P., Norwitz, E.R. et al. Metabolic Pathways Involved in 2-Methoxyestradiol Synthesis and Their Role in Preeclampsia. Reprod. Sci. 20, 1020–1029 (2013). https://doi.org/10.1177/1933719113477483

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