Non-serum PFAS biomarkers and human reproductive/perinatal outcomes: A systematic review.

Most epidemiologic evidence linking per- and polyfluoroalkyl substances (PFAS) to reproductive outcomes relies on serum biomarkers, which may not accurately reflect exposure in target reproductive compartments. We systematically reviewed literature (1 Jan 2020 - 31 Dec 2025) investigating PFAS in non-serum matrices (follicular fluid, placenta, semen, human milk, urine, and hair). Following PRISMA 2020 guidelines, we identified 58 eligible studies (19 primary associations; 39 biomonitoring/mechanistic). Study quality was assessed via the Newcastle-Ottawa Scale, with most association studies rated as 'Good.' While findings were heterogeneous across matrix-outcome domains, consistent signals emerged for follicular-fluid PFAS and impaired embryo quality, and placental PFAS and sex-dimorphic fetal growth restriction. Toxicokinetic data revealed high transfer efficiencies for PFOA into follicular fluid (0.72-0.94) but significant retention of PFOS in placental tissue. These findings suggest that non-serum biomarkers provide a time-resolved, compartment-specific perspective that offers greater etiological resolution than systemic serum measurements. Future research should adopt this "matrix-aware" framework to better characterize localized reproductive risks and improve environmental risk assessments.