Maternal-placental insulin-like growth factor (IGF) signaling and its importance to normal embryo-fetal development.

As background for an antibody-based therapeutic program against the IGF receptor, we undertook a review of available information on the early pregnancy-specific regulation and localization of IGFs, IGF-binding proteins (BPs), IGFBP-specific proteases, and the type 1 IGF receptor relative to placental maintenance, function of placental nutrient transporters, placental cellular differentiation/turnover/apoptosis, and critical hormone signaling needed to maintain pregnancy. Possible adverse outcomes of altered IGF signaling include prenatal loss, fetal growth retardation, and maldevelopment are also discussed. It appears that the IGF axes in both the conceptus and mother are important for normal embryo-fetal growth. Thus, all molecules (i.e., both small and large) that disrupt the IGF axis could be expected to have some degree of fetal consequences.