Transplacental transfer of metformin and interaction of metformin with the uptake transporters of placental trophoblast cells

Metformin is among the most widely prescribed antidiabetic agents, with increasingly accepted by women with gestational diabetes mellitus due to its more convenient administration. Knowledge of the interaction of metformin with the uptake transporters of placental trophoblast cells is important for robust evaluation of the safety usage in pregnancy. Herein, the pregnancy pharmacokinetic study and distribution in placenta and fetus study were employed and showed that metformin could distribute quickly into the placenta and fetus, and the content of MET in the placenta was obvious higher than that in fetus. We further explored the effect of the uptake transporters on the transmembrane movement of metformin in placental trophoblast cells, and found that OCT1, OCT2, OCT3, THTR1 and THTR2 may be involved in the transplacental transfer of metformin in BeWo cells and pregnant rats. Ulteriorly, the effect of metformin on the expression of nutrient uptake transporters was evaluated on BeWo cells, which indicated that metformin may affect the fetal uptake of related nutrients from maternal blood by affecting the expression of glucose transporters, amino acid transporters, fatty acids transporters and especially vitamin transporters on placental trophoblast cells. These findings could serve as a valuable reference for the clinical utilization of metformin in pregnant individuals.