Ogunleye, A. Z. | Search bioRxiv

bioRxiv2026

Epigenetic changes induced by developmental PFAS exposure in zebrafish associate with behavioral alterations in unexposed offspring

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with documented toxic effects, yet their multi- and transgenerational impacts on neurodevelopment and underlying mechanisms remain poorly understood. Here, we present a comprehensive study delineating the effects of developmental exposure to environmentally relevant concentrations of PFOS and PFBS on behavior, transcriptome, and genome-wide DNA methylation patterns in the directly exposed generation (F0) and their unexposed offspring (F1 and F2) in zebrafish. Both PFOS and PFBS altered larval behavior, linked to transcriptomic and DNA methylation changes in neuro-related pathways, even in the unexposed offspring. Importantly, specific DNA methylation changes in F0 were associated with behavioral outcomes in F2 animals, suggesting that these alterations could underlie transgenerational effects. Pathways associated with differentially methylated genes were prominently enriched for response to light and circadian regulation. Our findings demonstrate that developmental exposure to PFAS causes transgenerational behavioral effects in zebrafish and suggest that epigenetic changes induced by direct exposure may serve as markers for predicting outcomes in subsequent, unexposed generations. TEASERPFAS induce circadian-related epigenetic changes in zebrafish associated with behavioral impacts in unexposed offspring.

molecular biology↗

bioRxiv2025

Temporal structure of chemical stress controls single-cell inhibition and recovery in photosynthetic microorganisms

Although fluctuating conditions are a hallmark of microbial habitats, how the timing of chemical stress influences single-cell inhibition and recovery is not well resolved. Using a microfluidic platform, we continuously tracked photosynthetic performance in thousands of individual cells of a coral-associated microalga (Symbiodiniaceae sp.) exposed to identical cumulative doses of the photosystem II inhibitor diuron delivered either as constant or fluctuating profiles. Fluctuating exposure produced stronger early inhibition than constant exposure, but as concentrations declined it enabled partial recovery that did not occur under time-averaged constant conditions. These dynamics revealed distinct response subpopulations that differed in both the magnitude and timing of inhibition, including groups that regained activity exclusively under fluctuating stress. Quantifying per-cell decline kinetics showed that fluctuating exposure synchronizes the onset of inhibition across cells, creating a narrow temporal window in which a subset of cells can recover once stress levels fall, whereas constant exposure yields more heterogeneous but uniformly declining trajectories. These results demonstrate that stress timing, not cumulative dose alone, governs whether photosynthetic inhibition is reversible at the single-cell level. More broadly, our findings illustrate how temporal variability and intrinsic phenotypic heterogeneity jointly govern cellular function, highlighting stress timing as an important and often overlooked axis shaping microbial performance in dynamic environments. Significance statementEnvironmental stress in nature is rarely constant; instead, it fluctuates over minutes to days. Yet most laboratory assays rely on static exposures, leaving the role of stress timing poorly understood. Using microfluidics, we imposed precisely timed chemical stress on individual cells of a coral-associated microalga and monitored their photosynthetic performance continuously. Fluctuating exposure caused strong initial inhibition but later allowed partial recovery in a subset of cells, revealing functional heterogeneity that constant stress concealed. These results show that when stress occurs, its temporal structure can be as important as how much stress is delivered. By uncovering mechanisms that govern reversibility and heterogeneity in a key coral symbiont, this work provides a mechanistic basis for understanding microbial responses in dynamic environments.

ecology↗