Background: Per- and polyfluoroalkyl substances (PFAS) exert endocrine disruptive effects on the endocrine-metabolic axis. Emerging knowledge suggests that kisspeptin may play a key role in these effects.
Objective: To assess the cross-sectional association of blood PFAS concentrations with kisspeptin levels, KISS1 gene DNA methylation, and metabolic-related biomarkers in adolescent males from the Spanish INMA-Granada cohort.
Methods: Seven PFAS and twelve biomarkers (glucose-GLU, total cholesterol-TC, triglycerides, LDL, HDL, ALP, AST, ALT, GGT, total bilirubin-BILT, direct bilirubin-BILD, and urea) were measured in plasma and serum, respectively, from 129 adolescent males (15-17 yrs). Systolic and diastolic blood pressure (SBP, DBP), pulse, z-scored body mass index, kisspeptin protein levels (n = 104) and whole blood KISS1 DNA methylation (n = 117) were determined. Linear regression models, weighted quantile sum (WQS), and Bayesian kernel machine (BKMR) were fit.
Results: PFHpA was associated with lower GLU levels [% change per log-unit increase in plasma concentrations (95%CI) = -4.73 (-8.98;-0.28)], and PFUnDA with higher GLU, TC, and HDL levels. In models adjusted by kisspeptin level, PFOS was associated with higher SBP [3.42 (-0.12; 7.09)]. Additionally, PFNA and total PFAS concentrations were associated with higher kisspeptin levels [3.91 (0.55; 7.37) and 6.14 (0.47; 12.13), respectively]. Mixture models showed that combined PFAS exposure was associated with higher HDL, lower hepatic biomarkers (ALT, BILD) and higher kisspeptin levels.
Conclusion: Certain PFAS (e.g. PFUnDA) and their mixture were associated with metabolic-related biomarkers, mainly GLU, HDL, and SBP. These associations may be influenced by kisspeptin levels. More studies are needed to verify these observations.
Keywords: Effect biomarker; Endocrine disrupting chemicals; Kisspeptin; Metabolic marker; PFAS.
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