Regulation of decidualization, interleukin-11 and interleukin-15 by homeobox A 10 in endometrial stromal cells.

Cytokine production by the endometrial stromal and decidual cells is essential for successful differentiation of the endometrial stromal cells and uterine leukocytes to sustain pregnancy. Interleukin-11 and -15 (IL-11 and IL-15) secreted by the stromal and decidual cells are two key modulators of the process of decidualization and natural killer cell (NK) activity in the uterus and are essential for pregnancy. However, limited information exists on the maternal factors that regulate the production of these cytokines by the stromal cells. In this study, we investigated the role of homeobox A10 (HOXA10) in the regulation of expression of genes encoding the decidualization markers insulin-like growth factor binding protein-1 (IGFBP1), prolactin and the cytokines IL-11 and IL-15 by endometrial stromal and decidual cells in vitro. The results demonstrated that the expression of IGFBP1, Prolactin (PRL), HOXA10, IL11, and IL15 are co-regulated during steroid hormone-mediated decidualization of human endometrial stromal cells in vitro. In the predecidual cells, downregulation of HOXA10 by siRNA suppresses IGFBP1 and IL15, but increases IL11 expression. In the decidualized cells, knocking down HOXA10 inhibits IGFBP1 and PRL expression but elevates the expression of IL11 and IL15. In addition, our data also demonstrate that transient inhibition of HOXA10 expression in the predecidual cells does not influence its ability to subsequently decidualize or affect cytokine expression, suggesting that steroid hormone-mediated decidualization and cytokine production in vitro does not require HOXA10 preconditioning.