Mesenchymally-derived Insulin-like growth factor 1 provides a paracrine stimulus for trophoblast migration

Abstract

Background: Trophoblast migration into maternal decidua is essential for normal pregnancy. It occurs in a defined time window, is spatially highly restricted, and is aberrant in some pathological pregnancies, but the control mechanisms are as yet ill-defined. At the periphery of the placenta, chorionic villi make contact with decidua to form specialised anchoring sites that feed interstitially migrating cytotrophoblast into the placental bed.

Placental villous mesenchymal cells trigger trophoblast invasion

“…These factors may either restrain or promote EVT migration through the ligands produced by EVT. The third group contains the factors derived from placental villous mesenchyme that include IGF-I 12 and hepatocyte growth factor (HGF), 8 etc. These factors play as paracrine factors that trigger the EVT migration and modulate the distance of their invasion 12 ( Fig.…”

“…Such a signal diminishes with distance as the EVT migrate away the anchoring villus and is self-limiting when the in situ decidual factor eventually inhibit the stimulatory signal. 12 The placental villous stroma expresses HGF and its receptor c-Met is present in the trophoblasts. HGF is known to stimulate trophoblast motility via phosphatidylinositide 3-kinase and mitogen-activated protein-kinase signaling cascades.…”

The IGF Axis and Placental Function

“…A role for IGFs in regulating trophoblast migration was first suggested by data from monolayer wounding [21] and trans-Matrigel barrier assays [22] which demonstrated that both ligands can enhance trophoblast migration and invasion [23, 24]. Interestingly, although IGFs influence the migration of extravillous trophoblasts they have no effect on extravillous mitogenesis [22].…”

“…IGF-I is known to regulate both the differentiation of cytotrophoblasts into syncytiotrophoblast [26, 27] and into extravillous cells [23, 24], but there are no reports to implicate IGF-II in regulating placental cell differentiation. However, there are data to suggest that IGF-II may have a role in regulating nutrient exchange.…”

Maternal growth factor regulation of human placental development and fetal growth

“…Placentally derived IGF2 also has a role in promoting trophoblast invasion (Hamilton et al 1998), reportedly by inhibiting molecules such as IGFBP1 and TIMP3 that are produced by the decidua to constrain trophoblast infiltration of maternal tissues (Irwin et al 2001). Similarly, IGF1 from the villous mesenchyme provides a paracrine stimulus for extravillous trophoblast migration (Lacey et al 2002).…”