Decreased Maternal Serum 2-Methoxyestradiol Levels are Associated with the Development of Preeclampsia

Cellular Physiology and Biochemistry

关键词: 2-ME;    COMT;    Preeclampsia;    Trophoblast;    Cell proliferation and migration;   

DOI  :  10.1159/000369662

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background 2-methoxyestradiol (2-ME), a natural metabolite of 17β-estradiol, is synthesized by catechol-O-methyltransferase (COMT). The aim of this study was to explore the maternal 2-ME concentration and placental COMT expression in the different trimesters of normal pregnancy and preeclamptic pregnancies, as well as the effects of 2-ME on cell proliferation and migration of HTR-8/SVneo under normoxic (20% O₂) and hypoxic (2.5% O₂) conditions. Methods 2-ME levels were examined by ELISA. COMT protein expression was analyzed by Western blot and immunohistochemistry. Cell proliferation and migration were measured by crystal violet assay and transwell system under either normoxia or hypoxia. Results Maternal 2-ME concentration was elevated with the progression of pregnancy, in contrast, 2-ME was lower in women diagnosed with mild preeclampsia (mPE; 23%) and severe preeclampsia (sPE; 32%) as compared with normotensive full term pregnancies. Meanwhile, preterm controls had lower levels of 2-ME than full term controls. Soluble cytoplasmic COMT (S-COMT), but not membrane-bound COMT (MB-COMT) levels in placentas were increased by 2.5 fold in the full term vs. the first trimester placentas. Furthermore, 2-ME suppressed cell proliferation under 20% O₂ but not 2.5% O₂, while 2-ME promoted cell migration under 2.5% but not 20% O₂in vitro. Conclusion Considering 2.5% O₂ is a state more closely mimicking in vivo condition, these data suggest a decrease in 2-ME levels may inhibit trophoblast cell migration, possibly leading to PE.

【 授权许可】

CC BY-NC-ND