From Maternal Exposure to Fetal Risk: Unraveling the PFAS Exposure Pathway and Its Placental Toxicity Mechanism

Per- and polyfluoroalkyl substances (PFAS) have triggered a global crisis due to their severe toxicities and widespread occurrence in human populations. Notably, PFAS is frequently detected in maternal blood, placental tissue, and umbilical cord blood, indicating direct fetal exposure to PFAS through the maternal-fetal interface. As the central organ regulating nutrient exchange, endocrine signaling, and immune balance, the placenta is particularly vulnerable to PFAS exposure, and its dysfunction is linked with various adverse pregnancy outcomes, including fetal growth restriction, low birth weight, preterm birth, preeclampsia, etc. However, existing knowledge on PFAS-induced placental dysfunction remains fragmented, typically addressing their occurrence, transplacental transfer, specific mechanistic targets, or epidemiological evidence in isolation. This review synthesizes evidence tracing the entire trajectory of PFAS exposure─from maternal uptake and distribution in the bloodstream to placental accumulation, transplacental passage, and fetal exposure. It further highlights how PFAS may interfere with key processes of placental development, including angiogenesis and vascular remodeling, trophoblast migration and invasion, lipid metabolism, hormone production, and establishment of the maternal-fetal immune microenvironment, which provides mechanistic explanations linking PFAS exposure to adverse pregnancy outcomes. By integrating transplacental behaviors, mechanistic insights, epidemiological findings, and methodological advances, this review offers a comprehensive perspective on PFAS-induced placental toxicity and presents new directions for assessing maternal-fetal health risks.