Uterine stromal cell decidualization is integral to successful embryo implantation which is gateway to pregnancy establishment. This process is characterized by stromal cell proliferation and differentiation into decidual cells with polyploidy. Although various signaling molecules including cyclin D3 (a cell cycle regulator), HB-EGF (a heparinbinding EGF-like growth factor) and Hoxa-10 (a homeotic protein) are implicated in decidualization, the precise mechanisms by which these factors regulate this process and whether they are critical to decidualization are not known, except the essential role of Hoxa-10 in this process. We hypothesize that the success of decidualization is dependent on a balance between positive and negative regulators, directing proliferation and differentiation essential to this process;a tipping of this balance will lead to defective decidualization. We propose that Hoxa-10 and HB-EGF signaling converge to a common downstream cell cycle regulatory circuitry consisting of a positive cell cycle regulator cyclin D3 and negative cell cycle regulator cyclin G1 to appropriately balance proliferation and differentiation for achieving full complement of decidualization.
Our proposed research addresses an important concern of women's health i.e., infertility. Despite significant developments in IVF technology, the pregnancy success rate remains low because of higher incidence of implantation failure and unexplained pregnancy loss. In this respect, basic research as addressed in the present study to better understand molecular mechanisms that participate during implantation/decidualization is critical to ensure healthy pregnancy outcome.
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