Adverse adult-onset and multigenerational effects in zebrafish (Danio rerio) developmentally exposed to polystyrene nanoplastics

Microplastic (MP) and nanoplastic (NP) pollution has permeated virtually all aspects of life on earth - from high altitude clouds and arctic ice cores to single celled algae and unborn fetuses. Compared to MPs, the ability of NPs to infiltrate biological barriers such as the blood-brain and testes barriers is concerning to human health. Evidence of accumulation across human tissues has accrued, but the long-term health consequences are not well understood. Previously, we exposed zebrafish larvae to environmentally relevant doses of NPs (0-10,000 parts per billion) for five days during early development, reporting NP accumulation, hyperactivity, and disruption of neuromuscular, metabolic, and epigenetic pathways immediately post-exposure. Here, we reared these developmentally exposed animals to adulthood, assessing reproductive capacity, offspring neurobehavior, and transcriptomics of brain and gonadal tissue for comparison. NP exposure impaired reproduction in adulthood: while high level exposure profoundly reduced overall spawning capacity, intermediate exposure also decreased fertilization of elicited eggs. Surviving offspring from the intermediate group were also hyperactive, like their parents, demonstrating a persistent and heritable neurobehavioral phenotype. Overall, far more significantly differentially expressed genes were found in adult tissues than in larvae; however, larval disruption of endocrine and neurological disease pathways persisted into adulthood. While female transcriptomics suggested recovery from early life NP exposure, male tissues were deleteriously and disproportionately affected. Male transcriptomics implicated neuromuscular and neurodegenerative diseases, endocrine disruption, and cancer. Oxidative stress was a consistently present mechanism underlying persistent disruption and adult-onset pathologies.