Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish

• Published in: Toxicology and applied pharmacology 2017-08, Vol.329 (C), p.148-157
• Main Authors: Knecht, Andrea L., Truong, Lisa, Marvel, Skylar W., Reif, David M., Garcia, Abraham, Lu, Catherine, Simonich, Michael T., Teeguarden, Justin G., Tanguay, Robert L.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Aryl hydrocarbon receptor; Behavior, Animal - drug effects; Benzo(a)pyrene - toxicity; Benzo[a]pyrene; Developmental toxicity; DNA Methylation - drug effects; DNA Modification Methylases - metabolism; Dose-Response Relationship, Drug; ENVIRONMENTAL SCIENCES; Epigenesis, Genetic - drug effects; Genotype; Heart Rate - drug effects; Heredity; Inheritance Patterns - drug effects; Learning - drug effects; Mitochondria - drug effects; Mitochondria - metabolism; Motor Activity - drug effects; Neurobehavioral; Neurotoxicity Syndromes - genetics; Neurotoxicity Syndromes - metabolism; Neurotoxicity Syndromes - physiopathology; Phenotype; Physiological deficits; Repressor Proteins - agonists; Repressor Proteins - deficiency; Repressor Proteins - genetics; Respiration - drug effects; Risk Assessment; Social Behavior; Time Factors; Transgenerational; Water Pollutants, Chemical - toxicity; Zebrafish; Zebrafish - genetics; Zebrafish - growth & development; Zebrafish - metabolism; Zebrafish Proteins - agonists; Zebrafish Proteins - deficiency; Zebrafish Proteins - genetics
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2017.05.033

Benzo[a]pyrene (B[a]P) is a well-known genotoxic polycylic aromatic compound whose toxicity is dependent on signaling via the aryl hydrocarbon receptor (AHR). It is unclear to what extent detrimental effects of B[a]P exposures might impact future generations and whether transgenerational effects might be AHR-dependent. This study examined the effects of developmental B[a]P exposure on 3 generations of zebrafish. Zebrafish embryos were exposed from 6 to 120h post fertilization (hpf) to 5 and 10μM B[a]P and raised in chemical-free water until adulthood (F0). Two generations were raised from F0 fish to evaluate transgenerational inheritance. Morphological, physiological and neurobehavioral parameters were measured at two life stages. Juveniles of the F0 and F2 exhibited hyper locomotor activity, decreased heartbeat and mitochondrial function. B[a]P exposure during development resulted in decreased global DNA methylation levels and generally reduced expression of DNA methyltransferases in wild type zebrafish, with the latter effect largely reversed in an AHR2-null background. Adults from the F0 B[a]P exposed lineage displayed social anxiety-like behavior. Adults in the F2 transgeneration manifested gender-specific increased body mass index (BMI), increased oxygen consumption and hyper-avoidance behavior. Exposure to benzo[a]pyrene during development resulted in transgenerational inheritance of neurobehavioral and physiological deficiencies. Indirect evidence suggested the potential for an AHR2-dependent epigenetic route. [Display omitted] •Developmental exposure to benzo[a]pyrene results in transgenerational effects.•Neurobehavioral and physiological functions impacted across multiple generations.•B[a]P decreases global DNA methylation and DNA methyltransferase expression.•Behavioral methylation and gene changes are AHR2-dependent.