Sex-specific associations of per- and polyfluoroalkyl substances with brain-derived neurotrophic factors (BDNF) in cord serum.

Background: Per- and polyfluoroalkyl substances (PFAS) is perceived as an emerging environmental endocrine disruptor, which have been linked to children neurodevelopment. However, the potential mechanisms are not clear. Brain-derived neurotrophic factor (BDNF) is a vital protein in neurodevelopment, and the associations between PFAS exposure and BDNF require exploration.

Objective: We aimed to explore the relationships between PFAS exposure and the levels of BDNF in cord serum.

Methods: A total of 1,189 mother-infant dyads from the Sheyang Mini Birth Cohort Study (SMBCS) were enrolled. The levels of 12 PFAS and BDNF were measured in cord serum. We utilized generalized linear models (GLMs), quantile-based g-computation (QGC) models, and Bayesian Kernel Machine Regression (BKMR) models to explore the relationships between single and mixed PFAS exposure and BDNF concentration. Additionally, the potential sex differences were explored by sex-stratified analysis.

Results: Median concentrations of the included 10 PFAS ranged from 0.04 to 3.97 μg/L. In the single chemical models, four PFAS congeners, namely perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), were negatively associated with BDNF levels in cord serum among females only (β: -0.116 to -0.062, p < 0.05). In the BKMR models of total mother-infant dyads and female fetuses, the significant negative relationships between PFAS mixtures and BDNF were observed, and PFUnDA was identified as an important contributor (Posterior inclusion probability, PIP = 0.8584 for the total subjects; PIP = 0.8488 for the females). PFOS was another important driver based on the mixture approaches.

Conclusions: We found that PFNA, PFOS, PFDA, and PFUnDA were associated with decreased BDNF concentration in the females, although the causal inference might be limited. PFAS mixtures were also negatively linked with BDNF levels in the total mother-infant pairs and female fetuses. The adverse effect of PFAS exposure on fetal BDNF levels might be sex-specific.