Objectif Implantation failure after natural mating or in vitro fertilization may be due to either embryo or endometrial factors. Recent evidence suggests that sub-clinical infection, inflammation or malfunctions of the immune system in the female reproductive tract (FRT) are major causes of implantation failure. Toll like receptors (TLRs) have been shown to have a key role in the induction of immune and inflammatory responses in mammals. TLRs are the main family of pattern recognition receptors, they recognise pathogen-associated molecular pattern and constitute a major part of the innate immune system. We have demonstrated the presence and distribution of TLRs in the human FRT and we have also reported cyclical expression of TLRs during the menstrual cycle in the human endometrium. TLRs expression and function is also affected by sex hormones in endometrial cell lines. Finally using in vitro assays of human implantation, it is clear that activation of TLR5 leads to a reduction in binding of human trophoblast cells to endometrium. Indicative of the role that this molecule plays in mediating human implantation process. We aim to systemically investigate the effect of sex hormones on expression and function of TLR5 in Human endometrial cells. We hypothesise that alteration of sex hormones in the environment of endometrial cells will result in alterations of TLR5 expression and function. Using a TLR5 gene-reporter system, TLR5-eGFP system and microfluditics we aim to construct an in vitro model for systemic analysis of TLR5 gene expression, protein production and function in endometrial cells in the presence of different combinations and concentrations of sex hormones. Data obtained will be used to establish an in silico model to predict alterations in expression and function of TLR5 at different stages of reproductive cycle, in health and disease. Such an in silico model will have diverse applications in improving diagnosis, treatment and care for infertility patients. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencescomputer and information sciencesartificial intelligencepattern recognitionnatural sciencesbiological scienceszoologymammalogymedical and health sciencesclinical medicineembryology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2009-IIF - Marie Curie Action: "International Incoming Fellowships" Appel à propositions FP7-PEOPLE-2009-IIF Voir d’autres projets de cet appel Régime de financement MC-IIF - International Incoming Fellowships (IIF) Coordinateur THE UNIVERSITY OF SHEFFIELD Contribution de l’UE € 173 240,80 Adresse FIRTH COURT WESTERN BANK S10 2TN Sheffield Royaume-Uni Voir sur la carte Région Yorkshire and the Humber South Yorkshire Sheffield Type d’activité Higher or Secondary Education Establishments Contact administratif Joanne Watson (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
