Role of the Insulin-like growth factor axis and the Transforming growth factor-β in the regulation of the placenta and the pathogenesis of Gestational Trophoblastic Diseases

Abstract

During human pregnancy, the trophoblast develops as the fetal compartment, while in bidirectional communication with the maternal decidua. The trophoblast is responsible for the adequate implantation of the embryo, supply of nutrients and environmental protection of the fetus along the progress of pregnancy. To perform these functions trophoblast cells, undergo a complex and finely tuned differentiation into specialized groups of cells, in a process regulated by several hormones, growth factors and cytokines. Abnormalities in trophoblast function result in several pregnancy complications. In this review, we focus our attention on two growth factors with pivotal roles during human pregnancy. The Insulin-like growth factor (IGF) family and the Transforming growth factor (TGF-β) axis are important regulators of the proliferation, differentiation, apoptosis, migration and invasion of human trophoblasts. We summarize what is described in the literature on how these factors and their receptors are expressed on the different subsets of trophoblasts, the signaling pathways that transduce their corresponding actions and functional biological effects. We describe the associations that have been found between these growth factors and the group of pathologies known as Gestational Trophoblastic Diseases (GTD).

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“…70 Insulin-like growth factors belong to a family of peptides essential for fetal growth and development, and may also play a role as a modulator of cell growth in fetal membranes and placenta via autocrine/paracrine mutual actions and the uterine decidua has been considered as its location of action. 71 Umana-Perez et al 72 believed that IGF-1 and TGF-β (Transforming growth factor-β secreted by the maternal decidua and by the placenta and highly expressed only during the first trimester of pregnancy) play oppositely key roles in the regulation of human placenta growth. IGF-1 role is to promote the multiplication and differentiation of trophoblastic cells, while the TGF-β role is to limit the invasion of trophoblastic cells.…”