REGULATION OF CELL DIFFERENTATION DURING DECIDUALIZATION

University Of Illinois At Chicago, Chicago IL

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Abstract

One of the most remarkable processes associated with the establishment of pregnancy in the primate is the process of decidualization. This transformation of a stromal fibroblast to a fully differentiated decidual cell is required for implantation and embryo survival in early pregnancy. Although the morphological and biochemical characteristics of the primate decidual cell have been extensively studied, the precise regulation and activation of signaling pathways required for this transformation have yet to be elucidated. Decidualization in baboon consists from the initial proliferative phase, followed by a differentiation phase The differentiation phase is characterized by the down-regulation of alpha-smooth muscle actin (alpha-smooth muscle actin (alpha-SMA) and expression of insulin-like growth factor binding protein-1 (IGFBP-1), the biochemical marker of decidualization in the baboon. This phase requires the presence of conceptus in vivo or stimulation with cAMP or interleukin-1beta (IL-1beta) in presence of hormones in vitro. This application focuses on the potential signaling pathways that are activated by IL-1beta, an important cytokine at maternal-fetal interphase. Decidualization requires active remodeling of the stromal cell and we will determine in specific aim 1 the role of matrix metalloproteinase-3 (MMP- 3) in this process. The role of the steroid hormones in inhibit excessive MMP-3 activity through retinoic acid will be addressed in Specific aim 2. The proposed studies will enable us to obtain basic data under defined in vitro cell culture conditions regarding the regulatory and signaling pathways at fetal/maternal interface during implantation. These results will form the basis for a future R01 application. The ultimate goal of our studies is a thorough understanding of the cellular and molecular changes that occur during implantation. We anticipate that our ongoing studies will contribute to find therapies to treat endometrial dysfunctions associated with infertility, habitual abortions and/or insufficient placental development.