"The multidisciplinary research teams in this consortium have played lead roles in establishing that fetal and childhood periods are vulnerable to environmental disruption leading to common reproductive disorders. This proposal will investigate: (1) connections between normal/abnormal perinatal reproductive development and maturation of reproductive function at puberty and in adulthood; (2) systemic gene-environment interactions underlying reproductive disorders taking account of genetic susceptibility, multiple exposures (e.g. mixtures of environmental chemicals) and their timing (perinatal, peripubertal, adult); (3) connection between perinatal reproductive development and later obesity/metabolic disorders. To achieve this we will utilize large cohorts generated in previous EU projects and collect new data from these on reproductive maturation and adult function. Existing genomic and proteomics data, exposure data for >100 potentially toxic environmental chemicals, lifestyle, dietary and medical history information will be analysed using integrative systems biology approaches to pinpoint critical (interacting) factors influencing development. Established animal models will be used to test putative mechanisms by analysing the roles of neuroendocrine regulation, intrauterine growth, time windows of reproductive development, metabolic balance and xenobiotic metabolism. Toxicogenomics, proteomics and metabolomics results from these studies will identify pathways for study in the human cohorts. The overall aim is to create new cause-effect frameworks and knowledge networks to refine research in this critical area and to identify novel biomarkers of exposure and disease. The proposed studies will facilitate prediction and prevention of reproductive disorders and provide large new datasets and exposure-outcome information to improve environmental risk assessment and risk management."