Source of angiopoietin-2 in the sera of women during pregnancy

Placental development requires coordinated angiogenesis regulated by multiple factors including angiopoietins. Previously we demonstrated that the concentration of angiopoietin-2 (Ang-2) in the sera of women rises markedly in pregnancy in early gestation. This increase is reduced in pregnancies subsequently complicated by intrauterine growth restriction (IUGR). We now show that the concentration of Ang-2, but not Ang-1, in maternal serum is increased during normal pregnancy, peaking at the end of the first trimester. We also demonstrate that a key source of the elevated Ang-2 levels during pregnancy is decidual endothelial cells (DECs) but not cytotrophoblasts. Secretion of Ang-2 by DECs relies on the release from intracellular stores and the synthesis of new Ang-2 protein and is regulated by serum factors at a translational level. Further studies on the role of Ang-2 during pregnancy are warranted as well as the evaluation of Ang-2 as a marker to predict adverse pregnancy outcomes. ► Ang-2, but not Ang-1, is elevated in maternal serum compared to non-pregnant serum. ► The key source of the elevated Ang-2 during pregnancy is decidual endothelial cells. ► Ang-2 release by DECs relies on intracellular stores and newly synthesized protein. ► The pregnancy-induced rise in Ang-2 in maternal sera is attenuated in IUGR.