@misc{10481/71076,
year = {2022},
month = {1},
url = {http://hdl.handle.net/10481/71076},
abstract = {Background: Bisphenol A (BPA) exposure has been linked to altered behavior in children. Within the European Human Biomonitoring Initiative (HBM4EU), an adverse outcome pathway (AOP) network was constructed supporting the mechanistic link between BPA exposure and brain-derived neurotrophic factor (BDNF). Objective: To test this toxicologically-based hypothesis in the prospective INMA-Granada birth cohort (Spain). Methods: BPA concentrations were quantified by LC-MS/MS in spot urine samples from boys aged 9-11 years, normalized by creatinine and log-2 transformed. At adolescence (15-17 years), blood and urine specimens were collected, and serum and urinary BDNF protein levels were measured using immunoassays. DNA methylation levels at 6 CpGs in Exon IV of the BDNF gene were also assessed in peripheral blood using bisulfite-pyrosequencing. Adolescent's behavior was parent-rated using the Child Behavior Checklist (CBCL/6-18) in 148 boys. Adjusted linear regression and mediation models were fit. Results: Childhood urinary BPA concentrations were longitudinally and positively associated with thought problems (beta = 0.76; 95% CI: 0.02, 1.49) and somatic complaints (beta = 0.80; 95% CI: -0.16, 1.75) at adolescence. BPA concentrations were positively associated with BDNF DNA methylation at CpG6 (beta = 0.21; 95% CI: 0.06, 0.36) and mean CpG methylation (beta = 0.10; 95% CI: 0.01, 0.18), but not with total serum or urinary BDNF protein levels. When independent variables were categorized in tertiles, positive dose-response associations were observed between BPA-thought problems (p-trend = 0.08), BPA-CpG6 (p-trend <_ 0.01), and CpG6-thought problems (p-trend <_ 0.01). A significant mediated effect by CpG6 DNA methylation was observed (beta = 0.23; 95% CI: 0.01, 0.57), accounting for up to 34% of the BPA-thought problems association. Conclusions: In line with toxicological studies, BPA exposure was longitudinally associated with increased BDNF DNA methylation, supporting the biological plausibility of BPA-behavior relationships previously described in the epidemiological literature. Given its novelty and preliminary nature, this effect biomarker approach should be replicated in larger birth cohorts.},
organization = {Instituto de Salud Carlos III},
organization = {"Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER)	MS16/00085},
organization = {Sara Borrell postdoctoral research contract grant	CD17/00212},
organization = {Spanish Government	FPU 16/03011- FPU 17/01848},
organization = {Ramon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain)	RYC-2016-20155},
organization = {Human Genotyping Laboratory at the Spanish National Cancer Research Centre, CeGen-PRB3	PT17/0019},
organization = {Instituto de Salud Carlos III
European Commission},
organization = {European Commission},
publisher = {Elsevier},
keywords = {Bisphenol A},
keywords = {Brain-derived neurotrophic factor},
keywords = {Neurodevelopment},
keywords = {Adolescence},
keywords = {Biomonitoring},
keywords = {HBM4EU},
title = {BDNF as a potential mediator between childhood BPA exposure and behavioral function in adolescent boys from the INMA-Granada cohort},
doi = {10.1016/j.scitotenv.2021.150014},
author = {Mustieles Miralles, Vicente and Rodríguez Carrillo, Andrea and Vela Soria, Fernando and D'Cruz, Shereen Cynthia and David, Arthur and Smagulova, Fátima and Mundo López, Antonio and Olivas Martínez, Alicia and Reina Pérez, Iris and Olea Serrano, Nicolás and Freire, Carmen and Arrebola Moreno, Juan Pedro and Fernández Cabrera, Mariana Fátima},
}