Developmental exposure to PFAS mixture suppresses genes associated with neural cell development in adulthood: Neurod1 as a predicted transcriptional regulator

Title : Developmental exposure to PFAS mixture suppresses genes associated with neural cell development in adulthood: Neurod1 as a predicted transcriptional regulator

Abstract:

Background: Per- and PolyFluoroAlkyl Substances (PFAS) are a class of persistent man-made chemicals, often referred to as “forever chemicals,” that have been detected in water, human tissues, and wildlife globally. The two most prevalent PFAS, PerFluoroOctanoic Acid (PFOA) and PerFluoroOctane Sulfonic Acid (PFOS), have been linked to neurotoxicity by epidemiologic and animal studies, but the effects of a PFOA/PFOS mixture remains understudied. This study investigated the lasting transcriptomic effects of developmental PFOA/PFOS mixture exposure on adult zebrafish, an animal model sharing ~70% of their genome with humans.
Methods: Zebrafish embryos were exposed from 0-5 days post-fertilization to environmentally relevant concentrations of PFOA, PFOS, or a mixture of both. Fish were raised to adulthood (~18 months) and brain tissue was collected for 3'mRNA sequencing. Differentially expressed genes were identified and Ingenuity Pathway Analysis was performed to identify potential upregulators and disease associations.
Results: In mixture-exposed adult male zebrafish brain, there were 5304 differentially expressed genes and 327 dysregulated disease pathways compared to the controls. These genes were associated with multiple neurological pathways including neural cell development, seizure activation, and memory disorders that were significantly changed. Of interest, important upstream regulators essential for neurogenesis and nervous system formation (NEUROD1), and neuronal survival and dopaminergic neuron support (BDNF) were differentially expressed.
Conclusion: Developmental PFAS exposure may suppress neural cell development pathways in adulthood through NEUROD1 mediated transcriptional dysregulation, representing a public health concern and identifying NEUROD1 as a novel candidate mechanism for PFAS-induced neurodevelopmental toxicity.

Biography:

Sarah Acra is a dual-degree student at the University of Florida Honors program. She is currently pursuing her Bachelor of Health Science and Master of Public Health and is a research assistant at the UF Genetics Institute, where she researches how aquatic contaminants affect human health. She recently presented her work at UF’s Emerging Pathogens Institute Research Day 2026, where she won 1st place for undergraduate poster presentation. She is interested in public policy and is currently developing a health literacy course for students at her university. Before college, she wrote a children’s book to raise awareness for autism.