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Perfluorooctanoic acid toxicity on zebrafish embryonic development and mechanism exploration with single-cell RNA sequencing

ABSTRACT: The aquatic environment is an important site for perfluorooctanoic acid (PFOA) deposit and induced a high risk for aquatic organisms. Nevertheless, the current toxicity assessment was rarely reported the heart effect of PFOA. The exact mode of action and its resulting heterogeneity toxicological effects in aquatic organisms also remain largely unknown. In this study, the heart effects were investigated with a series of assays. The scRNA-seq showed nine cells populations were significantly altered with PFOA exposure. Heart was the mostly influenced cells and the function of cardiac muscle contraction, gas transport and oxygen binding was significantly changed. Moreover, the hatching gland cells, macrophages and lens cells were also significantly influenced with the altered function of apoptosis, endocrine and nervous and immune system. In addition, a significantly decreased swimming behavior and heart morphogenesis were verified.

ORGANISM(S): Danio rerio

PROVIDER: GSE176853 | GEO | 2022/08/01

REPOSITORIES: GEO

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Project description:Perfluorooctanoic acid (PFOA) is one of the most used perfluorinated compounds in numerous applications and can be detected in environmental samples from around the globe. The aquatic environment is an important site for PFOA deposit. Nevertheless, the exact mode of action and its resulting toxicological effects on aquatic organisms remain largely unknown. To gain a more extensive understanding of the mode of action of teleost PFOA toxicity, transcriptomics, proteomics, biochemical parameters and reproduction were integrated in the present study. Male and female zebrafish were exposed to nominal concentrations of 0.1; 0.5 and 1 mg/l PFOA for 4 and 28 days resulting in an accumulation which was higher in males compared to females. These gender-related differences were likely caused by different elimination rates due to distinct hormone levels and differences in transport activity by solute carriers. The general mode of action of PFOA was believed to be an increase of the mitochondrial membrane permeability which caused effects on the electron transport system at the biochemical level and resulted in alterations of the oxidative phosphorylation, oxidative stress and apoptosis at the gene transcript and protein level. As a consequence, evidence for the replacement of the affected cells and organelles to sustain tissue homeostasis was found at the molecular level. The higher energy demand, due to these adverse effects, was provided by lowering the glycogen stores. Despite this increase in metabolic expenditure, no effects on reproduction were found indicating that the fish seemed to cope with exposure to the tested concentrations of PFOA. Adult zebrafish (Danio rerio) were exposed to nominal concentrations of 0mg/l; 0.1mg/l; 1mg/l PFOA (perfluorooctanoic acid) for 28 days. Three different 25 litre aquaria per exposure concentration were used resulting in 3 biological replicates with each aquarium containing 8 male and 8 female zebrafish. The livers of 6 male fish and 6 female fish were pooled separately and snap frozen in liquid nitrogen. A reference sample was made by pooling equal amounts of RNA from all samples. A carriage wheel design was used in which all samples were connected to the reference sample and the main contrasts of interest were made directly on the same microarrays as frequently as possible. This design resulted in technical triplicates of each sample.