title: Decreased maternal serum 2-methoxyestradiol levels are associated with the development of preeclampsia.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Laboratory Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Shen
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.forename: Xinwen
authors.initials: X
authors.lastname: Chang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Tao
authors.initials: T
authors.lastname: Duan
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
mesh_terms: D000077584:2-Methoxyestradiol; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000097:blood* / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006801:Humans; D010920:Placenta / Q000473:pathology; D011225:Pre-Eclampsia / Q000097:blood* / Q000473:pathology; D011247:Pregnancy; D011261:Pregnancy Trimester, First
chemical_list: D004958:Estradiol; D000077584:2-Methoxyestradiol; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase