Folic acid uptake by the human syncytiotrophoblast: Interference by pharmacotherapy, drugs of abuse and pathological conditions

Folic acid (FA) is crucial for fetal development. We aimed to study the modulation of FA placental uptake by: hyperserotoninemia and hyperglycaemia, anti-hypertensives, insulin and drugs of abuse. For this, we characterized 3H-FA uptake by primary cultures of human cytotrophoblasts (TB cells) and tested the effects of these compounds upon 3H-FA uptake, TB cell viability and gene expression. Our results show that: (a) acutely, 3H-FA uptake was decreased by labetalol (0.1–1000 μM), ecstasy and amphetamine (0.025–25 μM); and (b) chronically, 3H-FA uptake was decreased by high glucose (30 mM), atenolol, nicotine (0.1 and 10 μM), ethanol (0.01 and 10 mM), ecstasy, amphetamine (0.25 and 1 μM) and tetrahydrocannabinol (1 and 100 nM). Moreover, many of these drugs were cytotoxic and they differentially modulated the mRNA expression of FA placental transport systems. Our results suggest that inhibition of FA placental uptake may constitute one of the mechanisms involved in the fetotoxicity of many of the compounds tested.