Acute and chronic effects of some dietary bioactive compounds on folic acid uptake and on the expression of folic acid transporters by the human trophoblast cell line BeWo

Folic acid (FA) is a vitamin that acts as a coenzyme in the biosynthesis of purine and pyrimidine precursors of nucleic acids, which are critically important during pregnancy. Our group has previously shown that both reduced folate carrier (RFC1) and folate receptor α (FRα) seem to be involved in the uptake of [3H]folic acid ([3H]FA) by a human trophoblast cell line (BeWo) and by human primary cultured cytotrophoblasts. Our aim was to study the interaction between FA and some nutrients/bioactive substances. For this, we tested the acute and chronic effects of some dietary compounds on [3H]FA apical uptake and on the expression of both RFC1 and FRα mRNA in BeWo cells. Our results show that [3H]FA uptake was significantly reduced by acute exposure to epicatechin, isoxanthohumol (1–400 μM) or theophylline (0.1–100 μM); isoxanthohumol seemed to act as a competitive inhibitor, whereas epicatechin and theophylline caused an increase in both Km and Vmax. On the other hand, [3H]FA uptake was significantly increased by chronic exposure to xanthohumol, quercetin or isoxanthohumol (0.1–10 μM), and this increase does not seem to result from changes in the level of RFC1 or FRα gene expression. Moreover, [3H]FA uptake was significantly reduced by chronic exposure to ethanol (0.01%). This reduction seems to be, at least in part, due to a reduction in FRα expression. These results are compatible with an association between a deficient FA supply to the placenta/fetus and ethanol toxicity in pregnancy.