Aim of the study: Implantation of a developmentally competent embryo in a receptive uterus is an essential process during the establishment of pregnancy in mammals. Based on the current knowledge, it is assumed that improper implantation is the cause of 75% of failed pregnancies. Synchronized activity of steroid hormones estrogen (E) and progesterone (P) through their nuclear receptors is the key for successful pregnancy. Mechanisms of E and particularly P-regulated pathways during implantation still need to be clarified. The aim of this research was to determine progesterone receptor’s (PR) role in the establishment of pregnancy in vivo using a mouse model organism. I investigated: 1. spatiotemporal relationship between PR and its targets: Hand2, COX2, ER and FGF9 during the periimplantation period; 2. spatial changes in the expression of PR-regulated genes during implantation; 3. changes in expression of Hand2, COX2, FGF9 and PR genes at the implantation site in relation to the non-implantation site and 4. steroid hormone regulation of Hand2 and FGF9 expression. Material and methods: For these studies BALB/c mice were used. Immunofluorescence analyses of uterus tissue obtained from pregnant mice were used to study the spatiotemporal relationship between PR and PR-regulated genes during peri-implantation. Changes in the expression of PR regulated genes at the implantation site in relation to the non-implantation site were analyzed by using immunofluorescence on uterus tissue, as well as using quantitative real time-PCR (RT-PCR). Differences in Hand2 and FGF9 gene and protein expression during periimplantation were determined by using RT-PCR as well as by western blot. To study the regulation of Hand2 and FGF9 gene expression by steroid hormones in the uterus, ovariectomized WT mice were hormonally treated. The role of PR isoforms in Hand2 expression was studied by using E and P treated ovariectomized PRAKO and PRKO mice. Results: During peri-implantation period the expression of PR and PR regulated genes Hand2, COX2, ERα and FGF9 dynamically changes in the uterus and is highly cell specific. Transcriptional activity of PR is necessary for the expression of Hand2 and COX2 in the specific population of the stromal cells at the implantation site. At the implantation site the expression of Hand2 and Cox2 was significantly higher in comparison to the non-implantation site. The expression of Hand2 is regulated by the PR-A isoform in endometrium. Transcriptional activity of ERα is downregulated at the implantation site. For the first time, this study showed that FGF9 is an important factor for the establishment of communication between a competent blastocyst and a receptive uterus. Conclusion: Balance in P and E regulated activity, throughout their cognate receptors is crucial to establish a suitable environment for embryo implantation in mice. The interaction of transcription factors PR and Hand2 is necessary for differentiation of specific stromal cells at the site of implantation. In these cells PR and Hand2 stimulate production of prostaglandins, which are the key mediators of angiogenesis and decidualization in the uterus. Growth factor FGF9 is an important factor for implantation and the establishment of pregnancy in the mice.