Environmental exposure to legacy poly/perfluoroalkyl substances, emerging alternatives and isomers and semen quality in men: A mixture analysis.

BACKGROUND/OBJECTIVES:Multiple studies have examined the relationship between PFAS and semen quality, but none has explored the associations of PFAS mixture that includes emerging alternatives and branched isomers. METHODS:22 PFAS, including 10 linear legacy PFAS, 7 branched isomers, 3 short chain alternatives and 2 components of F53B [e.g., 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA)] were quantified in blood plasma among 740 healthy men. Five semen quality parameters (i.e., volume, count, concentration, total motility and progressive rate) were assessed. Multiple linear regression and three multiple pollutant models (i.e., adaptive elastic net regression, quantile based g-computation, and XGBoost method) were used to assess the associations of individual PFAS and PFAS mixture with semen quality and the potential interactive effects among congeners. RESULTS:After adjusting for selected confounders, perfluorobutane sulfonate (PFBS) and perfluorohexane sulfonate (PFHxS) presented significant and negative associations with sperm count [βAENET = -0.09 (95%CI: -0.14, -0.03) for PFBS, and -0.16 (95%CI: -0.25, -0.07) for PFHxS] and sperm concentration [-0.04 (95%CI: -0.08, -0.001) for PFBS and -0.11 (95%CI: -0.17, -0.04) for PFHxS]. 6:2 Cl-PFESA showed negative associations with total motility (-2.33, 95%CI: -3.80, -0.86) and progressive rate (-1.46, 95%CI: -2.79, -0.12). But perfluoroheptanesulfonic acid (PFHpS) was positively associated with sperm count and concentration. These associations were supported by the importance assessment of these four congeners in XGBoost analyses. However, no associations were found between PFAS mixture or branched isomers and semen quality; nor were there significant interactions among PFAS congeners. CONCLUSIONS:In the current cross-sectional study, we found that two emerging PFAS replacements (i.e., 6:2 Cl-PFESA and PFBS) and PFHxS exposure were associated with reduced semen concentration, total sperm count and motility in men. Meanwhile, significant positive associations between PFHpS and sperm count and concentration were also observed. But there were no consistent associations between PFAS mixture, branched isomers and semen quality.