Transplacental transfer of the phytoestrogen daidzein in DA/Han rats
Transplacental transfer of the phytoestrogen daidzein in DA/Han rats
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DOI：
10.1007/s00204-001-0305-7
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发表时间：
2002-02-01
影响因子：
6.1
通讯作者：
Bolt, HM
中科院分区：
文献类型：
--
作者：
Degen, GH;Janning, P;Bolt, HM
在妊娠第 18 天的怀孕 DA/Han 大鼠中研究了植物雌激素大豆苷元的处置和经胎盘转移。静脉注射 10 mg/kg 体重后，在特定时间（5、10、20、40 和 120 分钟）通过 HPLC 测定母血、母体器官（肝、肾、子宫）、胎盘和胎儿（肝和残余组织）中的黄豆苷元浓度。注射后不久，大部分循环的黄豆苷元仍处于苷元形式；在后来的时间点，大多数由缀合物组成。母体血浆中最初的高异黄酮浓度（5 分钟时约为 25 微克/毫升）在第一小时内迅速下降，2 小时后总黄豆苷元低于 1 微克/毫升。尽管其结合效率很高，但黄豆苷元在生物体内迅速分布：在所有分析的组织中静脉注射后 10 分钟达到峰值浓度，母体肝脏中的平均值约为 31 微克/克，肾脏中为 13 微克/克，子宫中为 5 微克/克。胎盘中含有的黄豆苷元浓度约为肝脏的十分之一，胎儿肝脏中的黄豆苷元浓度约为母体肝脏峰值浓度的1/30（即1.3μg/g，是胎盘浓度的三分之一）。随后，组织中的大豆苷元水平与母血中的水平同步下降。数据显示，大豆苷元通过 DA/Han 大鼠的胎盘转移至胎儿。这表明从母亲到胎儿的快速转移，而且也表明肝脏从母体血液中有效提取大豆苷元。由于膳食植物雌激素在人类潜在内分泌调节剂暴露中占很大比例，而且胎盘并不代表大豆黄酮或相关雌激素异黄酮的屏障，因此应仔细检查和监测生命早期暴露这些暴露的后果。
Disposition and transplacental transfer of the phytoestrogen daidzein was studied in pregnant DA/Han rats on day 18 of gestation. Daidzein concentrations were determined by HPLC in maternal blood, maternal organs (liver, kidney, uterus), placenta and fetuses (liver and residual tissues) at specific times (5, 10, 20, 40 and 120 min) after intravenous administration of 10 mg/kg body weight. Early after injection, the majority of circulating daidzein was still in the aglycone form; at later time points the majority consisted of conjugates. The initially high isoflavone concentration in maternal plasma (about 25 mug/ml at 5 min) decreased rapidly within the first hour, and after 2 h total daidzein was below 1 mug/ml. Despite its efficient conjugation, daidzein was rapidly distributed in the organism: peak concentrations were attained 10 min after intravenous administration in all tissues analysed, with mean values of about 31 mug/g in maternal liver, 13 mug/g in kidneys and 5 mug/g in the uterus. Placenta contained about one-tenth the hepatic daidzein concentration, and fetal liver about 1/30 the peak concentration of maternal liver (i.e. 1.3 mug/g, which is one-third the placental concentration). Daidzein levels in tissues then declined in parallel with those in maternal blood. The data show that daidzein is transferred across the placenta of DA/Han rats to fetuses. This is indicative of a rapid transfer from the mother to the fetus, but also that efficient hepatic extraction of daidzein from the maternal blood occurs. Since dietary phytoestrogens account for a significant proportion of human exposure to potential endocrine modulators, and since the placenta does not represent a barrier to daidzein or related estrogenic isoflavones, the consequences of these exposures early in life should be examined and monitored carefully.