GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310402/primaryOK200TranscriptomicsDanio rerioExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310402GEOGSEfalsePhotoperiod perturbations impact perfluorohexane sulfonate (PFHxS) induced developmental toxicity [PFHxS-5day]Perfluorohexane sulfonate (PFHxS) is a persistent perfluoroalkyl substance with increasing scrutiny due to its widespread occurrence and potential for developmental neurotoxicity. In this study, we investigated how photoperiod - a critical regulator of circadian physiology- modulates PFHxS toxicity in zebrafish embryos. Photoperiods are highly relevant in today’s context, where artificial lighting, shift work, and time-zone travel increasingly disrupt natural light-dark cycles. To evaluate this variable, embryos were raised under either a standard 14-hour light:10-hour dark (14L:10D) cycle, constant darkness (24D) or constant light (24L) and simultaneously exposed to PFHxS across a concentration range (0.0025–25 µM) from 2 to 120 hours post-fertilization. Since 24L did not elicit any significant phenotypic differences, this photoperiod was excluded from further studies. LC-MS analysis revealed comparable PFHxS uptake across 24D and 14L: 10D photoperiods, ruling out bioaccumulation-induced differences. However, behavioral assays showed photoperiod-specific phenotypes, with hyperactivity during light epochs under 24D. PFHxS elevated melatonin levels under 14L:10D but reduced them under 24D, indicating circadian endocrine disruption. Transcriptomic analysis revealed greater PFHxS-induced dysregulation under 24D, including suppressed DNA replication and cell cycle pathways and increased oxidative stress. These effects coincided with elevated ROS, increased DNA damage, and reduced proliferation. Eye-specific studies revealed reduced retinal proliferating cells and photoreceptor (cone) length under 24D, but not 14L:10D, suggesting that aberrations in eye development may be a driver of phenotypes. Collectively, our findings highlight the critical role of environmental lighting in shaping toxicological outcomes and emphasize the need to incorporate photoperiod context into risk assessments.2026/07/01GSE310402GSM9295473GSM9295484GSM9295485GSM9295474GSM9295482GSM9295471GSM9295483GSM9295472GSM9295488GSM9295477GSM9295466GSM9295467GSM9295478GSM9295475GSM9295486GSM9295487GSM9295465GSM9295476GSM9295480GSM9295470GSM9295481GSM9295468GSM9295479GSM929546934622310402Danio rerio[41791196]