Folic acid uptake and its regulation in the placenta

Folates are crucial nutrients to the developing fetus, and being nutritionally essential, they must be obtained from the maternal blood through placental transport. The strict importance of folates to fetal and pregnancy health is well demonstrated by the fact that an inverse relationship is known to exist between folate status in pregnancy and the risk of neural tube defects. However, given the present policies of folate supplementation during pregnancy, there is an actual concern on the possible implications of excessive exposure to folates during pregnancy for the future health. The placental transport of folates is a complex process involving three different transport systems (folate receptor a, reduced folate carrier 1, and proton-coupled folate transporter) functioning in a coordinate manner to ensure the vectorial transfer of folates from maternal to fetal circulation. Current and emerging research on the molecular mechanisms of placental transport of folates and its regulation support the conclusion that the placental transport of folates may be compromised by several dietary substances, therapeutic agents, drugs of abuse, and markers of pathological conditions, which may in turn threaten, to some degree, the normal development and growth of the fetus.