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

Abstract

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 – 120 hours post fertilization (hpf) to 5 and 10 μM 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.

Zebrafish models for personalized psychiatry: Insights from individual, strain and sex differences, and modeling gene x environment interactions

“…As a relatively new model to study environmental epigenetics, the role of epigenetic mechanisms in zebrafish CNS responses remains unclear, although some interesting data begin to emerge (see (Lakstygal, de Abreu & Kalueff, ) for a recent review). For instance, exposure to a genotoxic compound benzo[a]pyrene during embryonic development causes social anxiety‐like behavior in adult zebrafish and hyper‐avoidance behavior in their F2 offspring, accompanied by reduced DNA methylation and down‐regulated methyltransferases (Knecht et al, ). Another epigenetic effect on zebrafish behavior is methylmercury exposure of F0 embryos that causes hyperactivity and visual deficits in F2 fish (Carvan et al, ).…”

Nitrate and nitrite exposure increases anxiety-like behavior and alters brain metabolomic profile in zebrafish

“…Swimming behavior, startle response, innate predator avoidance, and social cohesion was tested in individual fish between 14-17 days of treatment, using a zebrafish visual imaging system (zVIS) as previously described 32,33 . Briefly, in the free swim assay fish were placed in a tank with 1.7L of water and the data from the first minute was ignored.…”

“…Custom-built shuttle boxes were used to test learning with a modified protocol as previously described 32,34 . The programmed protocol of this active avoidance conditioning test was designed to condition the zebrafish to leave the compartment with blue light ("reject side") and swim to the dark side ("accept side", also referred to as the correct side).…”

Long-Term Exposure to Benzo[a]Pyrene Affects Sexual Differentiation and Embryos Toxicity in Three Generations of Marine Medaka (Oryzias Melastigma)

“…Meanwhile, Booc et al [14] also found that the decreased embryos fertilization and hatching success of Fundulus heteroclotus were caused by BaP exposure. Moreover, some studies suggest that the expression of key genes has changed in some important pathways, which promote the toxic effects of BaP in fish, especially at critical development and reproductive stages [15]. Sex ratio is an effective biomarker used for the assessment of EDCs on reproductive interference in fish and other organisms [16].…”