Stakes: Availability of adequate test model systems is essential to the development of risk assessment programmes for nuclear receptors-interacting compounds (NR-ICs) (drugs, industrial compounds, cosmetics, environmental contaminants and food components). Goal: The objective of the EXERA project is to develop novel 3D in vitro models of mouse tissues from five major organs for the pharmaco-toxicological analysis of Estrogen Receptors-Interacting Compounds (ER-ICs): liver, skin and bone (non reproductive systems), ovary and testis (male and female reproductive systems). Work content: This objective will be pursued through a Work Programme which allies an integrated scientific approach between innovative technologies such as the 3D-culture device, known as "Rotary Cell Culture System" (RCCS Technology adapted to the needs of this project), established transgenic mouse lines (estrogen-reporter mice, here called MOUSE-1) and genomic platforms for ER-ICs characterization. Our strategy is planned around 5 main points including, besides the mentioned technologies, multiple cell cultures quality controls, immortalisation control, cell banking and the use of specific markers of estrogenic action and cell differentiation/health, in order to obtain estrogen-responsive 3D-cultures of well differentiated mouse cells. Expected Results and Related Benefits: The corresponding work programme will be ensured by an important involvement of the whole partnership and by a high degree of coordination between 7 private and 3 public institutions. The expected results of our effort will be scientifically, socially and economically relevant: 1) application/adaptation of new 3D-culture technologies to cell cultures devoted to the study of ER-ICs; 2) constitution of a cell bank and, finally 3) a battery of differentiated 3D cell-based systems derived from estrogen-reporter mice for basic and applied research (e.g. pharmacology and toxicology), public use and industrial use.
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