Steroid hormone regulation of implantation

Steroid hormones Estrogen (E) and Progesterone (P) coordinate to regulate the process of embryo implantation, the process by which embryo attaches to the uterine epithelium. The uterus in response to the implanting embryo undergoes various changes to help create a suitable environment for the implanting embryo. E and P regulate this process in the uterus, by upregulating various downstream target genes. To date very little is known about the downstream targets of E and P and how these effect changes in the uterus to culminate in successful implantation. In order to identify these targets we have used microarray analysis. CCAAT enhancer binding protein beta (C/EBP beta) was identified as target of both E and P that helps in the uterine epithelial proliferation followed by participation in both uterine stromal cell proliferation and differentiation. These results are discussed in chapter I of the thesis. Ovarian E surge is necessary for implantation, which occurs in mice on day 4 evening. The current notion is that E plays minimal role in the process of decidualization. Our studies show prominent expression of aromatase, the key enzyme involved in E synthesis, in the pregnant uterus during decidual phase of gestation. Studies in chapter II of the thesis describe the spatiotemporal expression pattern of this enzyme and the critical role of aromatase in the process of decidualization. Lipid droplets in various organs are indicative of steroidogenic potential. Previous studies have shown occurrence of lipid droplets in the uterus during pregnancy. In chapter III we describe how P mediates the assembly of these lipid droplets at the stromal epithelial border and E surge that occurs on day four afternoon helps in the dispersal of these droplets, by regulating lipid binding proteins such as tail interacting protein of 47 kilo Daltons (TIP 47). The lipid droplets along with the associated proteins are recently termed as adiposomes. While the exact function of these adiposomes in the pregnant uterus is not known, there is emerging evidence that they participate in establishing a morphogen gradient and might play a similar role in the uterus in helping uterine epithelial and stromal communication.