The IGF system in in-vitro human decidualization

Abstract

Decidualization of endometrial stromal cells (ESCs) is critical for a successful pregnancy but the molecular mechanisms of the process are poorly understood. In this study, we investigated whether the insulin-like growth factor (IGF) network is involved in this cellular process. Expression kinetics of members of the IGF system was examined at both mRNA and protein levels during in-vitro decidualization of cultured human ESCs. We found a significant up-regulation of IGF-II as well as of IGF-I receptor and the A and B insulin receptor (InsR) isoforms. In addition, levels of the key adaptor proteins insulin receptor substrate 1 (IRS-1) and IRS-2 increased, suggesting a potential involvement of the IGF signalling pathway in the decidualization process. Expression of two IGF binding proteins, IGFBP-1 and IGFBP-4, which can inhibit IGF action, also increased. In order to determine whether IGF signalling was activated during decidualization, the phosphorylation status of the receptors and the adaptor proteins was estimated. Only IRS-2 was slightly phosphorylated in decidualized cells and was further activated by the addition of exogenous IGF-II. These results suggest that the IGF signalling pathway could play a crucial role in the functions of decidualized endometrial cells.

Roles of Progesterone Receptor A and B Isoforms During Human Endometrial Decidualization

“…IRS2, together with IRS1 and SHC1, is a key mediator for the downstream signaling pathways of both insulin and insulin-like growth factor 1 (IGF-1). The expression and phosphorylation of IRS2 increased in endometrial stromal cells during in vitro decidualization, suggesting that it is involved in the signaling mechanisms controlling this process (48). In the present study, we showed that silencing of IRS2 expression impairs HESC differentiation ( Figure 7C).…”

Effect of single post-ovulatory administration of levonorgestrel on gene expression profile during the receptive period of the human endometrium

“…The expression of IGF1 and its receptor are stimulated by estrogen, so it is thought that the actions of estrogen-induced cell growth are mediated, at least in part, by IGF1 (Murphy & Ghahary 1990). Meanwhile, IGF2 has been associated with the characteristic cellular differentiation of the secretory phase (Lopez et al 1996) with an increase in mRNA levels in the decidualization of ESC (Ganeff et al 2009). LNG continuously released into the endometrial cavity causes a downregulation of IGF1 mRNA and an increase in IGF2 (Rutanen et al 1997).…”

Association of G1057D variant of insulin receptor substrate-2 with endometriosis

“…IRS proteins are the major downstream effectors of the IGFs, and they play a critical role in determining the cellular response to IGF stimulation (20). In a recent study, Ganeff et al (21) showed that only IRS2, not IRS1, is phosphorylated in decidualized endometrial cells and is further activated by the addition of exogenous IGF2 (21). Because the IGFs utilize IRSs to transduce their signals in cells, the alteration of IRS2 expression might sensitize endometrial cells to IGF signals and promote the growth of ectopic endometrium on peritoneal surfaces, as found in endometriosis (22).…”