Members of the vascular endothelial growth factor (VEGF) family of growth factors and their receptors, including VEGF-A, placental growth factor (PlGF), VEGF receptor (VEGFR)-1, and VEGFR-2 with co-receptor neuropilin-1 (NRP-1), are known to play a crucial role in the normal development and maintenance of the morphofunctional features of the placenta, also contributing to the peculiar immune tolerance occurring during pregnancy. Indeed, an altered expression of VEGF family members and their receptors has been implicated in inadequate placentation and dysregulation of the immune tolerance in a variety of pregnancy complications, especially in maternal hypertensive disorders. Of note, a dysregulated immunological environment characterizes also pregnancies of women affected by different autoimmune diseases and displaying positivity for anti-Ro/SSA and anti-La/SSB autoantibodies. These women are at high risk of adverse pregnancies in which placental dysfunction seems to play a determinant role. Hence, the present study aimed to investigate the expression and localization of VEGF, PlGF, VEGFR-1, VEGFR-2, and NRP-1 in placentas from pregnancies of anti-Ro/SSA- and anti-La/SSB-positive women with autoimmune diseases by using immunohistochemistry. Our findings revealed a general decrease in the expression of VEGF members and their receptors in all the placental components of autoimmune disease cases compared to controls, although PlGF and VEGFR-2 showed more pronounced decrements. Collectively, our findings suggest that abnormalities in placental expression of VEGF family members and their receptors might be implicated in pathophysiological features of anti-Ro/SSA- and anti-La/SSB-positive pregnancies. • The expression of VEGF family members changes in placentas from anti-Ro/SSA and anti-La/SSB-positive pregnant women. • A dysregulation of the expression of VEGF, PlGF, and their receptors may underlie placental dysfunction in pregnant women with autoimmune diseases. • An in-depth knowledge of placental expression of the VEGF family members might help to develop novel preventive and/or therapeutic approaches.
Manetti et al. (2026) studied this question.