PFAS association with kisspeptin and sex hormones in teenagers of the HBM4EU aligned studies

• Published in: Environmental pollution (1987) Vol. 335; p. 122214
• Main Authors: Rodríguez-Carrillo, Andrea, Remy, Sylvie, Koppen, Gudrun, Wauters, Natasha, Freire, Carmen, Olivas-Martínez, Alicia, Schillemans, Tessa, Åkesson, Agneta, Desalegn, Anteneh, Iszatt, Nina, den Hond, Elly, Verheyen, Veerle, Fábelová, Lucia, Murinova, Lubica Palkovicova, Pedraza-Díaz, Susana, Castaño, Argelia, García-Lario, José Vicente, Cox, Bianca, Govarts, Eva, Baken, Kirsten, Tena-Sempere, Manuel, Olea, Nicolás, Schoeters, Greet, Fernández, Mariana F.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.10.2023
• Subjects: Effect biomarkers; HBM4EU; Kisspeptin; Medicin och hälsovetenskap; PFAS; Reproductive hormones; Kisspeptin; HBM4EU; Reproductive hormones; Effect biomarkers; PFAS
• ISSN: 0269-7491; 1873-6424; 1873-6424
• DOI: 10.1016/j.envpol.2023.122214

Exposure to Perfluoroalkyl acids (PFAS) can impair human reproductive function, e.g., by delaying or advancing puberty, although their mechanisms of action are not fully understood. We therefore set out to evaluate the relationship between serum PFAS levels, both individually and as a mixture, on the Hypothalamic-Pituitary-Gonadal (HPG) axis by analyzing serum levels of reproductive hormones and also kisspeptin in European teenagers participating in three of the HBM4EU Aligned Studies. For this purpose, PFAS compounds were measured in 733 teenagers from Belgium (FLEHS IV study), Slovakia (PCB cohort follow-up), and Spain (BEA study) by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) in laboratories under the HBM4EU quality assurance quality control (QA/QC) program. In the same serum samples, kisspeptin 54 (kiss-54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were also measured using immunosorbent assays. Sex-stratified single pollutant linear regression models for separate studies, mixed single pollutant models accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the mixture of the three most available (PFNA, PFOA, and PFOS) were fit. PFAS associations with reproductive markers differed according to sex. Each natural log-unit increase of PFOA, PFNA, and PFOS were associated with higher TT [18.41 (6.18; 32.31), 15.60 (7.25; 24.61), 14.68 (6.18; 24.61), respectively] in girls, in the pooled analysis (all studies together). In males, G-computation showed that PFAS mixture was associated with lower FSH levels [-10.51 (−18.81;-1.36)]. The BKMR showed the same patterns observed in G-computation, including a significant increase on male Kiss-54 and SHBG levels. Overall, effect biomarkers may enhance the current epidemiological knowledge regarding the adverse effect of PFAS in human HPG axis, although further research is warranted. [Display omitted] •The relationship of PFAS, reproductive hormones and kiss-54 levels was investigated.•Some PFAS were associated with higher TT levels in females.•The PFAS mixture (PFOA, PFOS, PFNA) showed the same trends in female.•PFAS were associated with lower hormones and higher SHBG in males.•PFAS mixture was also associated with higher kiss-54 in males.