Environmental UV Filters Threaten Human Neurodevelopment: Disruption of Central and Peripheral Nervous System Lineage Commitment via WNT Signaling Dysregulation

Abstract

Ultraviolet filters (UVFs) are extensively employed in personal care products, coatings, and food packaging materials, raising increasing concerns regarding developmental vulnerability due to their frequent detection in breast milk and amniotic fluid. This study systematically evaluated the developmental neurotoxicity of representative benzophenone, benzotriazole, and triazine UVFs using human embryonic stem cell (hESC) differentiation models. The dynamic trajectories of both central and peripheral nervous system (CNS and PNS) development were tracked, revealing that UVFs induced an imbalanced CNS/PNS lineage commitment, with UV-328 particularly causing disruptions through direct modulation of the WNT signaling pathway. In the PNS, 10 nM UV-328 significantly inhibited proliferation and migration in neural crest cells by preventing E-cadherin downregulation. Conversely, in the CNS, BP-3, UV-328, and BEMT promoted aberrant midbrain differentiation by upregulating FOXA2, LMX1A, CORIN, OTX2, and EN1 expression, while impairing late-stage dopaminergic neuron specification by downregulating TH. These findings elucidate the molecular mechanisms underlying benzophenone, benzotriazole, and triazine UVF-induced developmental neurotoxicity and underscore the critical need to evaluate the environmental impact and safety of UVFs during sensitive developmental stages. Additionally, this study highlights the potential links between UVF exposure and neurological disorders, emphasizing the importance of continued investigation in this field to inform environmental policies and public health strategies.