Objective One of the deepest unanswered biological questions is how new phenotypes arise in evolution. To address this question, I propose to investigate a major mammalian innovation: pregnancy. Phenotypic novelties of pregnancy include efficient placental delivery of nutrients and internal fetal development. When being established, these novelties were associated with major gene regulatory changes in the endometrium of the uterus. My preliminary studies in human endometrial cells suggest that aryl hydrocarbon receptor (AHR) regulates genes that are essential for placental development and maternal immunotolerance of the fetus. It is also known that AHR evolved endometrium-specific expression early in the mammalian ancestor and acquired the ability to repress estrogen signalling necessary for implantation only in placental mammals. Here, I propose to study the origination of novel endometrial gene regulatory networks of AHR. I will establish the full endometrial target gene sets of AHR in major placental lineages and a non-placental out-group (opossum). Potential AHR targets will be validated in endometrial cells using knockdowns and reporter assays. The results of this study will provide a paradigm for understanding how transcription factors integrate into a new cell-signalling network. The findings will also expand our knowledge of the mechanisms of AHR-mediated toxicity of dioxins in mammalian reproduction and may reveal new therapeutic targets for the treatment of female reproductive disorders such as preeclampsia and endometriosis. Fields of science medical and health sciencesclinical medicineobstetricsfetal medicinemedical and health sciencesbasic medicinephysiologynatural sciencesbiological scienceszoologymammalogymedical and health sciencesclinical medicineembryologynatural sciencesbiological sciencesreproductive biology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-RI - RI – Reintegration panel Coordinator TURUN YLIOPISTO Net EU contribution € 191 325,60 Address YLIOPISTONMAKI 20014 Turku Finland See on map Region Manner-Suomi Etelä-Suomi Varsinais-Suomi Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 191 325,60