Transplacental transfer of the phytoestrogen daidzein in DA/Han rats
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- Degen, G.H., Janning, P., Diel, P. et al. Arch Toxicol (2002) 76: 23. doi:10.1007/s00204-001-0305-7
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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 µg/ml at 5 min) decreased rapidly within the first hour, and after 2 h total daidzein was below 1 µg/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 µg/g in maternal liver, 13 µg/g in kidneys and 5 µg/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 µg/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.