Per- and polyfluoroalkyl substances (PFAS) in placental compartments: Histopathological and toxicological data integration in an Italian cohort

er- and polyfluoroalkyl substances (PFAS) are synthetic environmental contaminants with widespread industrial and consumer applications, characterized by strong chemical stability and environmental persistence. Recent studies have highlighted placental permeability to PFAS, though evidence of direct histopathological impairment remains limited. This study aimed to investigate potential associations between PFAS exposure and histopathological abnormalities in placental samples. A total of 23 at-term pregnant women were recruited from two hospitals in Italy as part of a multicenter study. Placental samples, divided into maternal (decidua) and fetal (villi) compartments, were analyzed for PFAS concentration and histopathological alterations. PFAS were detected in 95.7 % of samples. The most frequently detected PFAS were PFOS (88 %), followed by PFHxS (83 %), PFOA (83 %), PFBS (54 %) and PFHxA (54 %). Preliminary findings suggest variable PFAS concentrations among subjects, with histopathological examination revealing placental alterations of potential clinical relevance. The observed histopathological alterations, particularly in cases of malperfusion and angiogenesis changes, suggest that PFAS may contribute to placental dysfunction, potentially affecting pregnancy outcomes. In particular, it could be hypothesized that PFHxA could exert an adverse influence on placental angiogenesis, due to pre-placental hypoxia stimulating the angiogenesis and resulting in increased ramification and number of branches. While direct causative links remain to be fully elucidated, these results underscore the need for further investigations into PFAS-related placental effects and their implications for fetal development.