Transplacental transfer and biotransformation of genistein in human placenta.
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 180min following addition of genistein (10ng/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 180min 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.
Balakrishnan
B
B
The Liggins Institute, The University of Auckland, Grafton, Auckland, New Zealand. b.balakrishnan@auckland.ac.nz
Thorstensen
E B
EB
Ponnampalam
A P
AP
Mitchell
M D
MD
D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D019833:Genistein / Q000493:pharmacokinetics*; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D048789:Phytoestrogens / Q000493:pharmacokinetics; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D053719:Tandem Mass Spectrometry
D048789:Phytoestrogens; D019833:Genistein