By combining developmental assessments with advanced metabolomic profiling, the study reveals how early-life chemical stress rewires metabolism, disrupts growth programs, and leaves a hidden legacy of skeletal deformities.
Benzo[a]pyrene is a polycyclic aromatic hydrocarbon widely detected in aquatic environments worldwide. Although its toxicity to developing fish has been documented, most studies focus on immediate or single-generation effects. In natural ecosystems, however, early-life exposure often coincides with sensitive developmental windows, raising concerns about inherited impacts that may not become visible until later generations. Understanding whether and how these effects persist is critical for assessing long-term ecological risks and population resilience.
A study (DOI:10.48130/newcontam-0025-0022) published in New Contaminants on 19 January 2026 by Jiezhang Mo's team, Shantou University, demonstrates that early-life exposure to environmental pollutants can impose hidden, long-term biological costs that extend beyond directly exposed individuals.
Using a three-generation medaka model combined with high-resolution phenotyping and untargeted metabolomics, the researchers first exposed F0 embryos to benzo[a]pyrene (2.5–80 μg/L), then reared F1 and F2 offspring in clean water to isolate inherited effects; they quantified embryonic survivorship and hatching dynamics through 20 days post-fertilization, measured larval morphometrics (body length, eye pit, swim bladder, yolk sac edema, and pericardial cavity) and scored skeletal/body deformities (craniofacial, spinal, fin), and finally profiled embryo metabolites in F0 and F2 using LC–MS with stringent QC, multivariate analyses (PCA and OPLS-DA), differential metabolite screening (VIP > 1.0, p < 0.05, fold change ≥ 1.5 or ≤ 0.67), and KEGG pathway enrichment. These methods revealed that direct exposure in F0 caused strong, concentration-dependent embryotoxicity: mortality rose significantly from day 10 at 80 μg/L and day 13 at 40 μg/L, and by 20 dpf survival collapsed to 13.3% ± 4.9% at 80 μg/L (vs 92.5% ± 1.8% control), alongside delayed hatching (2 days at ≤10 μg/L; 3 days at higher doses) and sharply reduced hatching at the highest concentration (12.5% ± 5.5% at 80 μg/L). Although F1–F2 survivorship largely recovered, developmental toxicity persisted in larvae, with a consistent reduction in body length at 20 μg/L across F0–F2 and generation-specific organ changes (reduced eye pit in F0 and F2, reduced swim bladder only in F1, and enlarged pericardial cavity plus yolk sac edema in F0–F1). Structural damage also carried across generations: craniofacial and spinal deformities increased in F0 and remained elevated in descendants, with higher spinal curvature in F1 and F2 at 20 and 80 μg/L and craniofacial deformity persisting notably at 20 μg/L; fin deformity showed a significant spike only in F0 at 40 μg/L. Metabolomics corroborated a durable biochemical footprint—hundreds of metabolites shifted (233/254 DAMs in F0 at 2.5/20 μg/L; 86/752 DAMs in F2), 42 DAMs overlapped between F0 and F2 at 20 μg/L, and KEGG analysis mapped disruptions to detoxification (e.g., ABC transporters), metabolic homeostasis (purine/pyrimidine; taurine/hypotaurine), core developmental signaling (VEGF, PI3K-Akt, mTOR, FoxO, cAMP), and neurological/sensory pathways, with F2 showing a pronounced dose response (3 pathways altered at 2.5 μg/L vs 71 at 20 μg/L) and enrichment of oxidative-balance pathways (sulfur relay, thiamine, sulfur metabolism), while a shared 10-pathway "core signature" (including mTOR signaling, purine metabolism, ABC transporters, and neuroactive ligand–receptor interaction) pointed to persistent targets underlying multigenerational toxicity.
This study shows that embryonic exposure to benzo[a]pyrene leaves a metabolic imprint that persists across generations, driving developmental impairment and skeletal toxicity long after exposure ends. By revealing the metabolomic foundations of these inherited effects, the research highlights the importance of considering multigenerational outcomes in environmental protection strategies—and underscores the lasting biological legacy of early-life pollution.
