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BACKGROUND: Epidemiological evidence remains equivocal on the associations between environmentally relevant levels of per-/polyfluoroalkyl substances (PFASs) and human semen quality.

OBJECTIVES: We aimed to test whether the potential effects on semen quality could be better observed when seminal PFAS levels were used as an exposure marker compared with serum PFAS levels.

METHODS: Matched semen and serum samples from 664 adult men were collected from a cross-sectional population in China from 2015 to 2016. Multiple semen parameters were assessed, along with measurement of 16 target PFASs in semen and serum. Partitioning between semen and serum was evaluated by the ratio of matrix-specific PFAS concentrations. Regression model results were expressed as the difference in each semen parameter associated with the per unit increase in the In-transformed PFAS level after adjusting for confounders.

RESULTS: Perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and emerging chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were detected at their highest concentrations in both semen and serum, with median concentrations of 0.23, 0.10, and 0.06 ng/mL in semen, respectively, and a semen-to-serum ratio of 1.3:3.1. The between-matrix correlations of these PFAS concentrations were high (R=0.70-0.83). Seminal PFOA, PFOS, and 6:2 Cl-PFESA levels were significantly associated with a lower percentage of progressive sperm and higher percentage of DNA fragmentation (false discovery rate-adjusted p-values of <0.05). Associations between serum PFAS levels and semen parameters were generally statistically weaker, except for DNA stainability, which was more strongly associated with serum-based PFASs than with semen-based PFASs.

CONCLUSIONS: Our results suggest the potential for deleterious effects following exposure to 6:2 Cl-PFESA and other PFASs. Compared with serum PFAS levels, the much clearer association of seminal PFAS levels with semen parameters suggests its advantage in hazard assessment on semen quality, although the potential for confounding might be higher. Exposure measurements in target tissue may be critical in clarifying effects related to PFAS exposure.