Masami Nakanishi

Human placental transport and metabolism of all-trans retinoic acid in vitro

Summary All-trans retinoic acid (TRA), a natural form of vitamin A, is known to be botha morphogen and a teratogen. The purpose of this investigation is to determine how the human placenta regulates and modulates the transplacental transfer and metabolism of TRA using a dual recirculating perfusion system. Following four hours of exposure to TRA, all parameters were similar to the twohour control values. TRA was rapidly removed from the maternal perfusate, and appeared in the fetal perfusate in a time-dependent manner. The final concentrations at 240 minutes in the maternal and fetal perfusates were 100±14 and 26±9 ng/ml, respectively, while the placental concentration was 4520±1850 ng/g tissue. Ketoconazole, an inhibitor of oxidative metabolism, decreased the oxidative metabolites of TRA and increased TRA and its isomer (13 cis-retinoic acid). These results demonstrate that the human placenta has the ability to modulate the transfer and metabolism of TRA.