Roles of the Insulinlike Growth Factor Family in Nonpregnant Human Endometrium and at the Decidual:Trophoblast Interface

Abstract

The insulinlike growth factor (IGF) family is believed to be important in endometrial development during the menstrual cycle and in the process of implantation. The mitogenic, differentiative, and antiapoptotic properties of the IGFs and their binding proteins, as well as their spatial and temporal expression in cycling endometrium, suggest that they may participate in endometrial growth, differentiation, apoptosis, and perhaps angiogenesis. IGFBP proteases, which increase IGF bioavailability, have been localized to endometrial stromal cells and to the human cytotrophoblast and likely play important roles in endometrial, decidual, and trophoblast physiology. IGFBP-1 is a major protein product of nonpregnant endometrium during the mid-late secretory phase and occurs in abundance in decidua. Its roles as an IGF-binding protein and as a trophoblast integrin ligand suggest that it may have multiple roles in endometrial development and in interactions between the decidua and the invading trophoblast. Recent evidence suggests that it may have a role in the process of shallow implantation in the clinical disorder of preclampsia. In contrast to knowledge about the roles of IGF peptides, IGFBP proteases, and IGFBPs in normal endometrial development and early human pregnancy, little information is available regarding this family in abnormal endometrial development, in occult endometrial defects, and in uterine receptivity and nonreceptivity.

Elevated levels of decidual insulin‐like growth factor binding protein‐1 in cervical fluid in early and mid‐pregnancy are associated with an increased risk of spontaneous preterm delivery

“…19 To our knowledge, this is the first study examining whether elevated levels of decidua-derived phIGFBP-1 in cervical fluid among unselected, asymptomatic women during early pregnancy are associated with an increased risk of subsequent spontaneous PTD. About one-third of the invited women participated in this study.…”

Interferon-γ and tumor necrosis factor-α sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis

“…It has been shown that factors secreted by the invading trophoblast, such as human chorionic gonadotropin (hCG, CGB) and insulin-like growth factor (IGF)-II (IGF2), can modulate endometrial receptivity and the milieu at the implantation site (Giudice and Irwin, 1999;Licht et al, 1998;Fluhr et al, 2006). FasL (FASLG), typically inducing deathreceptor-mediated apoptosis, is secreted by first-trimester trophoblast cells and has been assumed to play a pivotal role in promoting a state of immune privilege during implantation (Abrahams et al, 2004;Uckan et al, 1997).…”

Differential effects of human chorionic gonadotropin and decidualization on insulin-like growth factors-I and -II in human endometrial stromal cells

“…Under the influence of different endocrine regulators, locally expressed and acting growth factors and cytokines are the main mediators during endometrial development (1,3,5,6). The insulin-like growth factor (IGF) system has been shown to be involved strongly in endometrial proliferation and differentiation, as well as during the process of implantation (4,5,(7)(8)(9)(10). In the human endometrium, the expression of IGF-I and -II is restricted to the stromal cells, showing unique changes during the menstrual cycle (5,8).…”

“…The insulin-like growth factor (IGF) system has been shown to be involved strongly in endometrial proliferation and differentiation, as well as during the process of implantation (4,5,(7)(8)(9)(10). In the human endometrium, the expression of IGF-I and -II is restricted to the stromal cells, showing unique changes during the menstrual cycle (5,8). Insulin-like growth factor-I seems to be expressed preferentially in the mid to late proliferative and early secretory phase and is therefore believed to mediate the mitogenic actions of E 2 (11)(12)(13)(14).…”