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首页> 外文期刊>Cellular Physiology and Biochemistry >Decreased Maternal Serum 2-Methoxyestradiol Levels are Associated with the Development of Preeclampsia
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Decreased Maternal Serum 2-Methoxyestradiol Levels are Associated with the Development of Preeclampsia

机译:孕妇血清2-甲氧基雌二醇水平降低与先兆子痫的发展有关

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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.
机译:背景:2-甲氧基雌二醇(2-ME)是17β-雌二醇的天然代谢产物,是通过儿茶酚-O-甲基转移酶(COMT)合成的。这项研究的目的是探讨正常妊娠和先兆子痫孕妇不同孕期母体2-ME的浓度和胎盘COMT的表达,以及2-ME对HTR-8 / SVneo细胞增殖和迁移的影响。常氧(20%O 2 )和低氧(2.5%O 2 )条件。方法:采用ELISA法检测2-ME水平。通过蛋白质印迹和免疫组化分析COMT蛋白表达。在常氧或低氧下,通过结晶紫测定和transwell系统测量细胞的增殖和迁移。结果:孕妇2-ME的浓度随着妊娠的进行而升高,相比之下,诊断为轻度先兆子痫(mPE; 23%)和重度子痫前期(sPE; 32%)的女性2-ME较血压正常的足月低怀孕。同时,早产对照的2-ME水平低于足月对照。与早期三个月的胎盘相比,在整个学期中,胎盘中的可溶性细胞质COMT(S-COMT)而非膜结合的COMT(MB-COMT)水平增加了2.5倍。此外,2-ME在20%O 2 但不抑制2.5%O 2 时抑制细胞增殖,而2-ME在2.5%但未抑制20%O < sub> 2 体外。结论:考虑到2.5%O 2 是更接近体内条件的状态,这些数据表明2-ME水平的降低可能抑制滋养层细胞迁移,可能导致PE。

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