Trophoblast uptake of DBP regulates intracellular actin and promotes matrix invasion

Early pregnancy is characterised by elevated circulating levels of vitamin D binding protein (DBP). The impact this on maternal and fetal health unclear but DBP present in the placenta, gene variants have been linked to malplacentation disorders such as preeclampsia. functional role placenta was investigated using trophoblastic JEG3, BeWo HTR8 cells. All three cell lines showed intracellular with increased expression nuclear localisation cells treated active form D, 1,25-dihydroxyvitamin (1,25D). When cultured serum mice lacking (DBP?/?), JEG3 no indicating uptake exogenous DBP. Inhibition membrane receptor for DBP, megalin, also suppressed Elimination DBP?/? or megalin inhibitor matrix invasion trophoblast associated accumulation G-actin. Conversely, treatment 1,25D enhanced invasion. This independent ERK phosphorylation, inhibition kinase from pregnant women, correlated concentration, lower first-trimester women who later developed These data show that involves actin-binding homeostasis. a potential marker placentation preeclampsia may provide therapeutic option improved health.