New light on early post-implantation pregnancy in the mouse: roles for insulin-like growth factor-II (IGF-II)?

Successful placental development and the associated changes to the decidual vasculature during early pregnancy are critical to pregnancy outcome. This study utilised immunohistochemistry to provide a photomicrographic account of trophoblast invasion, as well as the changes in the uterine vasculature in the decidua from days 5.5 to 10.5 of murine pregnancy. The pattern of trophoblast invasion during this time is particularly interesting because, unlike in humans, murine trophoblast giant cells (TGCs) do not invade the endometrium individually but remain in close contact with the expanding giant cell layer. Therefore, trophoblast cells are unlikely to play a direct role in remodelling the maternal vessels in early to mid pregnancy. Nevertheless, the decidual vessels appear to undergo extensive angiogenesis and remodelling to form a network of dilated vessels that presumably maximize placental blood supply. Importantly, the vessels closest to the conceptus lacked a smooth muscle layer throughout early pregnancy and therefore cannot strictly be described as spiral arterioles. TGCs may secrete molecules that can act to induce these vascular changes. Here we show that insulin-like growth factor-II (IGF-II) is expressed throughout early pregnancy in the entire conceptus including trophoblast cells, supporting its role in promoting early placental growth. In addition, the co-localisation of IGF-II and both IGF receptors in the developing blood vessels and/or adjacent stromal cells in the mesometrial, but not in the anti-mesometrial, decidua suggest that IGF-II, upon binding to one of these receptors, may play a role in both decidual angiogenesis and placental differentiation.