Hernández Antonio F, Romero-Molina Desirée, Gonzalez-Alzaga Beatriz, López-Flores Inmaculada, Lacasaña Marina
Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain; Instituto de Investigación Biosanitaria, ibs.GRANADA, Granada, Spain; CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Instituto de Investigación Biosanitaria, ibs.GRANADA, Granada, Spain; Statistics and Operations Research Department, Faculty of Sciences, University of Granada, Granada, Spain.
Chemosphere. 2025 Apr;374:144204. doi: 10.1016/j.chemosphere.2025.144204. Epub 2025 Feb 11.
The rising incidence of neurodevelopmental disorders has been associated with early-life exposure to environmental factors, particularly neurotoxicants like organophosphate compounds (OPCs), which can impact brain development and function. This study examined the relationship between prenatal exposure to OPCs and molecular biomarkers of neurotoxicity in cord blood from 398 mother-child pairs in the GENEIDA birth cohort (Southeastern Spain). Urine samples were collected in the first and third trimesters and analysed for metabolites of organophosphate pesticides (dialkylphosphates, DAPs) and flame retardants (OPFRs) using LC-MS/MS. Six neurotoxicity biomarkers-brain-derived neurotrophic factor (BDNF), neurogranin (Ng), ubiquitin C-terminal hydrolase L1 (UCHL1), neurofilament heavy chain (NFH), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B)-were measured in cord blood via multiplex analysis using Luminex xMAP technology. The results showed that higher levels of DAP metabolites in maternal urine, particularly those with dimethyl groups, were associated with increased GFAP levels in cord blood. OPFR metabolites correlated with elevated GFAP and UCHL1 levels. Sex-specific effects were observed: OPFR levels were linked to higher GFAP in boys, while higher DAP metabolites, particularly those with diethyl groups, were associated with elevated BDNF in girls. Additionally, higher levels of diphenyl phosphate, an OPFR metabolite, were linked to increased S100B in boys. These findings suggest sexually dimorphic effects of prenatal OPC exposure. These findings provide preliminary evidence of developmental neurotoxicity and suggest potential biomarkers in cord blood for early detection of neurodevelopmental deficits. Further studies, including neurobehavioral evaluations and brain imaging, are needed to better understand these molecular effects.
神经发育障碍发病率的上升与生命早期暴露于环境因素有关，尤其是有机磷化合物（OPC）等神经毒物，这些物质会影响大脑发育和功能。本研究调查了西班牙东南部GENEIDA出生队列中398对母婴脐带血中产前暴露于OPC与神经毒性分子生物标志物之间的关系。在孕早期和孕晚期收集尿液样本，并使用液相色谱-串联质谱法（LC-MS/MS）分析有机磷农药（二烷基磷酸酯，DAPs）和阻燃剂（OPFRs）的代谢产物。通过使用Luminex xMAP技术的多重分析测定脐带血中的六种神经毒性生物标志物——脑源性神经营养因子（BDNF）、神经颗粒素（Ng）、泛素C末端水解酶L1（UCHL1）、神经丝重链（NFH）、胶质纤维酸性蛋白（GFAP）和S100钙结合蛋白B（S100B）。结果表明，母体尿液中DAP代谢产物水平较高，尤其是含有二甲基的代谢产物，与脐带血中GFAP水平升高有关。OPFR代谢产物与GFAP和UCHL1水平升高相关。观察到了性别特异性效应：OPFR水平与男孩中较高的GFAP相关，而较高的DAP代谢产物，尤其是含有二乙基的代谢产物，与女孩中BDNF升高有关。此外，OPFR代谢产物二苯基磷酸酯水平较高与男孩中S100B增加有关。这些发现表明产前OPC暴露存在性别差异效应。这些发现为发育性神经毒性提供了初步证据，并提示脐带血中可能存在用于早期检测神经发育缺陷的生物标志物。需要进一步的研究，包括神经行为评估和脑成像，以更好地理解这些分子效应。
