Folic acid attenuates dexamethasone-induced placental growth restriction

Intrauterine glucocorticoid (GC) exposure is associated with disturbances in feto-placental growth. This study aimed to investigate whether folic acid supplementation can prevent dexamethasone (Dex)-induced feto-placental growth restriction.

Female C57BL/6J mice were subject to four different treatments, respectively: normal drinking water plus saline injection (NN), normal drinking water plus Dex injection (ND), drinking water supplemented with folic acid plus saline injection (FN), and drinking water supplemented with folic acid plus Dex injection (FD). Folic acid (100 µg/L) was administrated since 2 weeks before the mating and throughout pregnancy. Dex injection (100 µg/kg•d) was performed from E12.5 to E16.5. The placentas were collected at E17.5.

The parameters including placental and fetal weight, the maximum placental diameter, volume of junctional and labyrinthine zones, and vascular density in the ND group were significantly smaller compared to the NN group. Except the maximum placental diameter, each of the above parameters in the FD group was significantly larger compared to the ND group. The levels of glucocorticoid receptor (GR) protein, and endothelial growth factor A, C (VEGFA, VEGFC) and placental growth factor (PIGF) mRNAs were significantly lower in the ND group compared to NN group. The VEGFA and PIGF mRNA level in the FD group was significantly higher than that in the ND group, as well as VEGFA and VEGFC protein level.

Folic acid may attenuate Dex-induced restriction on placental growth by elevating the expression of VEGFA and PIGF, and further raising vascular density.