Exposição no útero aos PFAS e saúde cardiometabólica, hepática e reprodutiva da infância à vida adulta: Em direção a um ambiente livre de PFAS para proteger a saúde

EndPFAS is the first project exploring the impact of in-utero exposure to PFAS ? ubiquitous, persistent, bioaccumulative and toxic chemicals ? on cardiometabolic, liver and reproductive health, using multiple refined measures with high predictive values for later health and following a life-course perspective. This project will contribute to unravel the adverse health effects of these chemicals from early childhood to young adulthood and aid in the identification of the underlying mechanisms of these associations (Figure 1). This is fully aligned with the EU research agenda on environment and health and will be highly relevant for researchers, policy makers and society. EndPFAS ́s objectives are: Objective 1 (O1): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with cardiovascular and metabolic health outcomes from early childhood to young adulthood (WP1); Hypothesis 1: High exposure of the foetus to PFAS increases the risk of adverse cardiovascular and metabolic health outcomes. Specific objective 1.1 (O1.1): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with repeated cardiovascular and metabolic health outcomes (i.e., blood pressure, body mass index, body composition and fat distribution, metabolic and inflammatory biomarkers) from 4 to 18 years. Specific objective 1.2 (O1.2): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with early markers of arterial health (i.e., carotid intima media thickness) at 18 years. Objective 2 (O2): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with liver health outcomes from early childhood to young adulthood (WP2); Hypothesis 2: High exposure of the foetus to PFAS increases the risk of liver injury. Specific objective 2.1 (O2.1): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with repeated measurements of multiple liver enzymes, as predictors of liver dysfunction, from 4 to 18 years. Specific objective 2.2 (O2.2): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with a clinically relevant marker of liver injury (i.e., liver fibrosis) at 18 years. Objective 3 (O3): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with reproductive health in males from birth to young adulthood (WP3); Hypothesis 3: High exposure of the foetus to PFAS impairs male fertility. Specific objective 3.1 (O3.1): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with repeated measurements of inhibin B concentrations, as marker of testicular function, in males from birth to 18 years. Objective 4 (O4): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with cord blood differential DNA methylation at birth and epigenetic gestational age acceleration (WP4); Hypothesis 4: The toxic in-utero effects of PFAS might be explained by changes in DNA methylation and faster epigenetic aging. Specific objective 4.1 (O4.1): To assess the associations of in-utero exposure to PFAS mixture with cord blood differential DNA methylation at birth. Specific objective 4.2 (O4.2): To assess the associations of in-utero exposure to multiple PFAS, individually and as mixture, with epigenetic gestational age acceleration.