Association and binding interaction between per- and polyfluoroalkyl substances and maternal thyroid hormones: A case study based on a prospective birth cohort in Wuxi, China.

Background And Aim: The relationship between prenatal exposure to per- and polyfluoroalkyl substances (PFASs), a well-known endocrine disruptor, and thyroid hormones (THs) levels remains unclear. Therefore, this study aimed to investigate this relationship in a birth cohort during the second trimester.

Method: This prospective study included 562 pregnant women in the Wuxi Birth Cohort from 2019 to 2021 and quantified the serum concentrations of 23 PFASs and 5 THs. Multiple statistical models were used to assess the associations between individual or combined PFASs concentrations and THs, while molecular docking simulated the interactions between PFASs and four thyroid-related proteins.

Results: The median concentration of ∑PFASs was 71.91 ng/mL, with perfluorovaleric acid (PFPeA) (18.13 ng/mL) emerging as the predominant PFAS. Most PFASs were negatively associated with maternal free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels, whereas perfluorobutane sulfonate (PFBS) was positively correlated with TSH levels. A similar trend was observed in the weighted quantile sum (WQS) model, in which combined PFASs exposure was inversely associated with the FT4 and TSH levels. Molecular docking results showed that compared with TH natural ligand thyroxine (T4), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl- PFESA) exhibited relatively high binding affinity with thyroid-related proteins (-6.6 to -9.8 kcal/mol vs. T4: -5.6 to -8.6 kcal/mol). Furthermore, PFASs with medium chain lengths and sulfonic acid groups exhibited enhanced protein-binding properties.

Conclusion: PFASs exposure may affect THs homeostasis during pregnancy. Moreover, different types and concentrations of PFASs have different effects on THs in the maternal serum.