Associations between per- and polyfluoroalkyl substances and semen parameters: An updated systematic review and meta-analysis.
Environmental exposure to per- and polyfluoroalkyl substances (PFAS) rises concerns about male reproductive health. Despite a wide body of experimental evidence supporting the biological role of PFAS exposure in male reproductive effects, available epidemiological studies are variably consistent about this association. Four databases were searched up to July 13, 2025 (PROSPERO: CRD420251267798). The systematic review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included that assessed the association of PFAS on sperm outcomes. The primary effect measure was the Pearson correlation coefficient (r). Outcomes included sperm concentration, semen volume, total sperm count, motility, morphology, pH, and sperm DNA fragmentation, Fourteen studies including 7465 participants were included in this review. The results of meta-analyses indicate heterogeneous patterns of association, with PFAS mixtures showing limited associations with conventional semen parameters but demonstrating consistent inverse relationships with progressive motility (correlation scale [r] = -0.058, 95% confidence interval [CI]: -0.100 to -0.015) and sperm deoxyribonucleic acid (DNA) integrity (r = 0.141, 95% CI: 0.087-0.195). Individual congeners exhibited distinct association profiles, suggesting potential congener-specific effects on male reproductive function. The consistent association between increased DNA fragmentation across PFAS metrics suggest a possible role in unexplained male infertility and prompts further investigation.