INHIBITOR OF DNA BINDING PROTEIN 2 (ID2) MEDIATES THE ANTI-PROLIFERATIVE AND PRO-DIFFERENTIATION EFFECTS OF INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) ON HUMAN FIRST TRIMESTER TROPHOBLAST CELLS

In preeclampsia (PE), impaired trophoblast proliferation and differentiation are thought to cause abnormal placentation and subsequent clinical manifestations of the disease. IGF-1 influences trophoblast cell function, however the mechanisms of IGF-1’s action on trophoblasts is not well understood. ID2 is involved in trophoblast differentiation and implicated in many processes disrupted in PE including placental development, vascular differentiation, and angiogenesis. We hypothesized that IGF-1 regulates trophoblast proliferation and differentiation via ID2. Immortalized human first trimester trophoblast cells (HTR-8/SVneo) were treated with IGF-1 for 24 hours after serum starvation. ID2 mRNA and protein were measured, as well as trophoblast cell viability, proliferation, tube formation and migration. IGF-1 decreased ID2 expression in a dose-dependent manner. IGF-1 decreased trophoblast proliferation but increased cell viability, differentiation, and migration. ID2 overexpression mitigated the effects of IGF-1 on trophoblast cells. These data suggest IGF-1 can regulate trophoblast function through ID2 which could have implications for PE pathogenesis.