Interleukin-11 inhibits expression of insulin-like growth factor binding protein-5 mRNA in decidualizing human endometrial stromal cells.

Differentiation of endometrial stromal cells into decidual cells is essential for successful embryo implantation. Interleukin (IL)-11 signalling is critical for normal decidualization in the mouse. The expression of IL-11 and its receptors during the menstrual cycle, and the effect of exogenous IL-11 on the decidualization of human endometrial stromal cells in vitro, suggests a role for this cytokine in human decidualization. As the downstream target genes of IL-11 are also likely to be critical mediators of this process, this study aimed to identify genes regulated by IL-11 in decidualizing human endometrial stromal cells in vitro. Stromal cells isolated from endometrial biopsies were decidualized with 17beta estradiol (E) and medroxyprogesterone acetate (EP) in the presence or absence of exogenous IL-11, and total RNA used for cDNA microarray analysis and real-time RT-PCR. Microarray analysis revealed 16 up-regulated and 11 down-regulated cDNAs in EP + IL-11-treated compared with EP-treated cells. The most down-regulated gene was insulin-like growth factor binding protein-5 (IGFBP-5) (3.6-fold). Using real-time RT-PCR, IL-11 was confirmed to decrease IGFBP-5 transcript abundance 102-fold (P = 0.016; n = 6). No difference in IGFBP-5 immunostaining intensity was detected in stromal cells decidualized in the presence or absence of IL-11, and there was no effect of exogenous IGFBP-5 on the progression of steroid-induced in vitro decidualization. Interactions between IL-11 and its target genes, including IGFBP-5, may contribute to the regulation of decidualization and/or mediate communication between the decidua and invading trophoblast at implantation.