Insulin-like growth factor-I as a local regulator of proliferation and differentiated function of the human trophoblast in early pregnancy.

Abstract

In order to elucidate the role of insulin-like growth factor-I (IGF-I) in human placental growth and function, the effects of IGF-I on the proliferation and differentiation of trophoblasts were investigated using an organ culture system of early placental tissues. Explants of trophoblastic tissues obtained from 4-5-week or 6-12-week placentae were, respectively, cultured with or without IGF-I, in a serum-free condition. The effect of IGF-I on the proliferative activity of trophoblasts was examined by immunocytochemical techniques with a monoclonal antibody to proliferating cell nuclear antigen (PCNA), while the effect of IGF-I on the differentiated function of trophoblasts was assessed by determining the ability to secrete human chorionic gonadotropin (hCG) and human placental lactogen (hPL). In 4-5-week placentae, IGF-I and IGF-I receptor were almost exclusively localized in cytotrophoblasts and IGF-I augmented the proliferative activity of cytotrophoblasts without affecting the ability to secrete hCG and hPL. By contrast, in 6-12-week placentae, IGF-I and IGF-I receptor were localized in both cytotrophoblasts and syncytiotrophoblasts and IGF-I stimulated the secretion of hCG and hPL following the enhancement of the proliferative activity of trophoblasts. In column chromatography of the serum-free medium obtained following 5-day culture of early placental tissues, an elution peak of immunoreactive IGF-I was found in the fractions similar to the elution region of [125I]IGF-I. These findings suggest that IGF-I acts as an autocrine/paracrine factor in regulating early placental growth and function.