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PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression.

ABSTRACT: Polyfluorinated compounds (PFC) are a class of anthropogenic, persistent and toxic chemicals. PFCs are detected worldwide and consist of fluorinated carbon chains of varying length, terminal groups, and industrial uses. Previous zebrafish studies in the literature as well as our own studies have shown that exposure to these chemicals at a low range of concentrations (0.02-2.0μM; 20-2000ppb) resulted in chemical specific developmental defects and reduced post hatch survival. It was hypothesized that sub-lethal embryonic exposure to perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), or perfluorooctanoic acid (PFOA) would result in different responses with regard to morphometric, behavior, and gene expression in both yolk sac fry and larval zebrafish. Zebrafish were exposed to PFOS, PFOA, and PFNA (0.02, 0.2, 2.0μM) for the first five days post fertilization (dpf) and analyzed for morphometrics (5 dpf, 14 dpf), targeted gene expression (5 dpf, 14 dpf), and locomotive behavior (14 dpf). All three PFCs commonly resulted in a decrease in total body length, increased tfc3a (muscle development) expression and decreased ap1s (protein transport) expression at 5dpf, and hyperactive locomotor activity 14 dpf. All other endpoints measured at both life-stage time points varied between each of the PFCs. PFOS, PFNA, and PFOA exposure resulted in significantly altered responses in terms of morphometric, locomotion, and gene expression endpoints, which could be manifested in field exposed teleosts.

SUBMITTER: Jantzen CE

PROVIDER: S-EPMC5204304 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression.

Jantzen Carrie E CE Annunziato Kate A KA Bugel Sean M SM Cooper Keith R KR

Aquatic toxicology (Amsterdam, Netherlands) 20160331

Polyfluorinated compounds (PFC) are a class of anthropogenic, persistent and toxic chemicals. PFCs are detected worldwide and consist of fluorinated carbon chains of varying length, terminal groups, and industrial uses. Previous zebrafish studies in the literature as well as our own studies have shown that exposure to these chemicals at a low range of concentrations (0.02-2.0μM; 20-2000ppb) resulted in chemical specific developmental defects and reduced post hatch survival. It was hypothesized t ...[more]

PMID: 27058923

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Project description:BackgroundSetting health-protective standards for poly- and perfluoroalkyl substances (PFAS) exposure requires estimates of their population toxicokinetics, but existing studies have reported widely varying PFAS half-lives (T½) and volumes of distribution (Vd).ObjectivesWe combined data from multiple studies to develop harmonized estimates of T½ and Vd, along with their interindividual variability, for four PFAS commonly found in drinking water: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS).MethodsWe identified published data on PFAS concentrations in human serum with corresponding drinking water measurements, separated into training and testing data sets. We fit training data sets to a one-compartment model incorporating interindividual variability, time-dependent drinking water concentrations, and background exposures. Use of a hierarchical Bayesian approach allowed us to incorporate informative priors at the population level, as well as at the study level. We compared posterior predictions to testing data sets to evaluate model performance.ResultsPosterior median (95% CI) estimates of T½ (in years) for the population geometric mean were 3.14 (2.69, 3.73) for PFOA, 3.36 (2.52, 4.42) for PFOS, 2.35 (1.65, 3.16) for PFNA, and 8.30 (5.38, 13.5) for PFHxS, all of which were within the range of previously published values. The extensive individual-level data for PFOA allowed accurate estimation of population variability, with a population geometric standard deviation of 1.57 (95% CI: 1.42, 1.73); data from other PFAS were also consistent with this degree of population variability. Vd estimates ranged from 0.19 to 0.43L/kg across the four PFAS, which tended to be slightly higher than previously published estimates.DiscussionThese results have direct application in both risk assessment (quantitative interspecies extrapolation and uncertainty factors for interindividual variability) and risk communication (interpretation of monitoring data). In addition, this study provides a rigorous methodology for further refinement with additional data, as well as application to other PFAS. https://doi.org/10.1289/EHP10103.

Project description:The glutathione redox system undergoes precise and dynamic changes during embryonic development, protecting against and mitigating oxidative insults. The antioxidant response is coordinately largely by the transcription factor Nuclear factor erythroid-2 (Nrf2), an endogenous sensor for cellular oxidative stress. We have previously demonstrated that impaired Nrf family signaling disrupts the glutathione redox system in the zebrafish embryo, and that impaired Nrf2 function increases embryonic sensitivity to environmental toxicants. Here, we investigated the persistent environmental toxicant and reported pro-oxidant perfluorooctanesulfonic acid (PFOS), and its impact on the embryonic glutathione-mediated redox environment. We further examined whether impaired Nrf2a function exacerbates PFOS-induced oxidative stress and embryotoxicity in the zebrafish, and the potential for Nrf2-PPAR crosstalk in the embryonic adaptive response. Wild-type and nrf2afh318-/- mutant embryos were exposed daily to 0 (0.01% v/v DMSO), 16, 32, or 64 μM PFOS beginning at 3 h post fertilization (hpf). Embryonic glutathione and cysteine redox environments were examined at 72 hpf. Gross embryonic toxicity, antioxidant gene expression, and apoptosis were examined at 96 hpf. Mortality, pericardial edema, and yolk sac utilization were increased in wild-type embryos exposed to PFOS. Embryonic glutathione and cysteine redox couples and gene expression of Nrf2 pathway targets were modulated by both exposure and genotype. Apoptosis was increased in PFOS-exposed wild-type embryos, though not in nrf2a mutants. In silico examination of putative transcription factor binding site suggested potential crosstalk between Nrf2 and PPAR signaling, since expression of PPARs and gene targets was modulated by both PFOS exposure and Nrf2a genotype. Overall, this work demonstrates that nrf2a modulates the embryonic response to PFOS, and that PPAR signaling may play a role in the embryonic adaptive response to PFOS.

Dataset Information

PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression.

Publications

PFOS, PFNA, and PFOA sub-lethal exposure to embryonic zebrafish have different toxicity profiles in terms of morphometrics, behavior and gene expression.

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