Adenovirally mediated expression of insulin-like growth factors enhances the function of first trimester placental fibroblasts

Abstract

IGFs are critical in fetal growth because of their role in placental development and function. In this study, we used adenovirus (Ad-IGF) to deliver sense or antisense IGF-I or IGF-II cDNA to human primary placental fibroblasts (PPF) in vitro to determine whether this could lead to enhanced placental cell function. PPFs virally transfected with Ad-IGF-I or Ad-IGF-II showed 7-fold (P <0.01) and 3-fold (P <0.01) increases in [3H]thymidine incorporation at 48 h post infection compared with nontransfected controls. In a coculture system designed to assess cell migration, nontransfected PPF cells positioned over a monolayer transfected by Ad-IGF-I or AdIGF-II showed a more than 10-fold (P <0.01) and a 7-fold (P <0.01) increase in migration compared with cells positioned above a nontransfected monolayer. After 98 h in culture, PPFs transfected with sense Ad-IGF-I or Ad-IGF-II showed 2% apoptosis compared with 16% of nontransfected cells, whereas 37% and 25% of cells transfected with antisense Ad-IGF-I or Ad-IGF-II were apoptotic. This work has established that cells of placental origin are amenable to adenoviral transfection and that IGFs exert autocrine and paracrine effects on proliferation, migration, and survival, suggesting that enhancement of IGF levels in the placenta may augment placental function and increase fetal growth