Mitsuoki Asai

The Role of the Human Placenta in Embryonic Nutrition. Impact of Environmental and Social Factors

The human placenta has been implicated in the poor growth and development of the embryo/fetus due to alterations in blood flow and reductions in the transfer of nutrients such as amino acids and carbohydrates. Deficiencies of such nutrients have been the principal of many research investigations. The role of micronutrients, however, may also be major factors in appropriate growth and development, and there may be a general reduction in the availability of such nutrients, for example, the role of folate supplementation during early pregnancy and the reduction in the incidence of neural tube defects. Vitamins are not all transported via a common mechanism. Therefore, the modulation of human placental transport can be different for different vitamins, for example, A and B12. It is apparent that the human placenta can oxidatively metabolize retinoids (isotretinoin and tretinoin) to more toxic or less toxic metabolites. These metabolites can then be transferred to the fetal circulation. Such metabolism/transfer is in contrast to how vitamin B12 is bound to transcobalamin proteins, which are produced by the placenta and directionally released into the maternal and fetal circulations.

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.