Profiles of Emerging and Legacy Per-/Polyfluoroalkyl Substances in Matched Serum and Semen Samples: New Implications for Human Semen Quality

Abstract

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 ln-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.

Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

“…Exposure to PFOA impairs human sperm motility and sperm penetration into viscous media (Sabovic et al 2020; Yuan et al 2020) and is longitudinally associated with lower sperm concentration and count and higher adjusted levels of luteinizing and follicle‐stimulating hormones in young men (Joensen et al 2009; Vested et al 2013; Song et al 2018). Serum concentrations of PFAS are also cross‐sectionally associated with deleterious markers of semen quality (Louis et al 2015; Pan et al 2019).…”

Perfluoroalkyl Chemicals and Male Reproductive Health: Do PFOA and PFOS Increase Risk for Male Infertility?

“…A cross-sectional study on 212 exposed males from the Veneto region, Italy, found that increased levels of PFOA (but not PFOS) in serum and seminal fluids positively correlated with circulating testosterone and luteinizing hormone (LH), with a resultant reduction in semen quality, testicular volume, penile length, and anogenital distance [ 34 ]. A cross-sectional study from Nanjing, China [ 103 ], on 664 adult men showed that seminal PFOA and PFOS levels were significantly associated with a lower percentage of progressive sperm and higher percentage of DNA fragmentation. Use of serum PFOA and PFOS levels made their association weaker compared to the levels in seminal fluids [ 103 ].…”

“…A cross-sectional study from Nanjing, China [ 103 ], on 664 adult men showed that seminal PFOA and PFOS levels were significantly associated with a lower percentage of progressive sperm and higher percentage of DNA fragmentation. Use of serum PFOA and PFOS levels made their association weaker compared to the levels in seminal fluids [ 103 ]. A follow-up study [ 33 ] using the same population confirmed the association between serum and semen PFOA levels with semen parameters and showed a decrease in total testosterone and free testosterone.…”

N ‐acetyl cysteine co‐treatment abates perfluorooctanoic acid‐induced reproductive toxicity in male rats

“…PFOA is highly resistant to degradation by ecological processes, with a half‐life of 2.3–3.8 years in humans (Post et al., 2012; Shane et al., 2020; Taylor et al., 2020), with a significant cause of toxicity concern. Exposure sources include home‐grown vegetables, food and food packaging, house dust and consumer products (Choi et al., 2020; Post et al., 2012; Xiang et al., 2020), at environmentally relevant levels of 8–35 ng/L (ATSDR, 2018; Dong et al., 2009; Post, 2020), reported to be harmful to human sperm quality (Pan et al., 2019).…”

“…Exposure sources include home-grown vegetables, food and food packaging, house dust and consumer products (Choi et al, 2020;Post et al, 2012;Xiang et al, 2020), at environmentally relevant levels of 8-35 ng/L (ATSDR, 2018;Dong et al, 2009;Post, 2020), reported to be harmful to human sperm quality (Pan et al, 2019).…”