Molecular structure, isomerism, and concentration as determinants of PFAS transfer from plasma to ovarian follicular...

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent contaminants with emerging evidence of adverse reproductive health impacts. Although PFAS isomers exhibit distinct toxicological effects, their environmental occurrence and human biomonitoring remain poorly resolved, with branched isomers frequently undercharacterized. In this study, we quantified PFAS concentrations, identified homologous trends, characterized isomer profiles, and determined blood-follicle transfer efficiencies (BFTEs) in paired plasma and ovarian follicular fluid from 42 women undergoing infertility treatment. Linear PFAS isomers exhibited higher BFTEs and stronger correlations between plasma and follicular fluid concentrations than did their branched counterparts. These results confirm isomer-specific partitioning among perfluoroalkyl sulfonic acids, and establish that the phenomenon is even more pronounced in perfluoroalkyl carboxylic acids. Branched perfluorohexanonic acid (PFHxA) was documented for the first time in human plasma but virtually absent from paired follicular fluid. Perfluoro-4-methoxybutanoic acid (PFMBA) and 6:2 fluorotelomersulfonic acid (6:2 FTS) were more common in plasma than follicular fluid, further highlighting the importance of investigating the mechanisms underlying these differences. Perfluorohexanesulfonic acid (PFHxS) concentrations in patient plasma were approximately twice those reported in national and international cohorts, underscoring the need for geographically resolved biomonitoring. These findings demonstrate how molecular structure, including isomerism, constrains PFAS follicular fluid transfer and highlight the need for isomer-resolved biomonitoring to more accurately assess reproductive exposure risks. A more nuanced understanding of PFAS structure-partitioning relationships may help clinicians interpret plasma PFAS measurements in relation to follicular exposure and identify patients or regions that warrant intensified mitigation.