Transplacental Transfer and Biotransformation of Genistein in Human Placenta

Transplacental Transfer and Biotransformation of Genistein in Human Placenta
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DOI:
10.1016/j.placenta.2010.03.007
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发表时间:
2010-06-01
期刊:
影响因子:
3.8
通讯作者:
Mitchell, M. D.
Mitchell, M. D.
中科院分区:
医学3区
文献类型:
--
作者:
Balakrishnan, B.;Thorstensen, E. B.;Mitchell, M. D.

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目的:研究金雀异黄素在人胎盘中的经胎盘转移和生物转化。研究设计和结果:采用双循环体外胎盘灌流模型。4个胎盘在母体灌流液中加入金雀异黄素(10 ng/mL),灌流180min。分别以安替比林和FITC右旋糖苷为阳性对照和阴性对照验证电路的完整性。结果:金雀异黄素和安替比林的转运百分率分别为25.6+/-1.40%和22.1+/-1.61%,染料木素的转运指数为0.90+/-0.04。胎儿房室和母体房室分别有12.0+/-2.40%和7.36+/-4.73%的金雀异黄素以结合形式存在。结论:金雀异黄素可以在环境相关水平上通过胎盘转运。胎盘代谢酶结合一小部分染料木素形成葡萄糖醛酸/硫酸盐形式,这是没有雌激素作用的。(C)2010爱思唯尔有限公司。保留所有权利。
Objective: To study transplacental transfer and biotransformation of genistein in the human placenta.Study design and outcomes: Human placentae obtained from healthy term singleton pregnancies were utilised in a dual re-circulating model of ex-vivo placental perfusion. Four placentae were perfused for 180 min following addition of genistein (10 ng/mL) to the maternal perfusate. Antipyrine and FITC dextran were used as positive and negative controls respectively to validate integrity of the circuits. Concentrations of genistein and its conjugates were determined by liquid chromatography-mass spectrometry (LC-MS).Results: The transfer percentage for antipyrine and genistein was 25.6 +/- 1.40% and 22.1 +/- 1.61% respectively and the transfer index for genistein was 0.90 +/- 0.04 after 180 min of perfusion. 12.0 +/- 2.40% of genistein in the fetal compartment and 7.36 +/- 4.73% of genistein in the maternal compartment were in the conjugated form.Conclusions: Genistein can transfer across the human placenta at environmentally relevant levels. Placental metabolizing enzymes conjugate a small fraction of genistein into the glucuronide/sulphate form, which is devoid of estrogenic action. (C) 2010 Elsevier Ltd. All rights reserved.