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Transcriptomic analysis of adult zebrafish brain exposed developmentally to 2 concentrations of a persistent organic pollutants (POP) mixture or 2 concentrations of PFOS (0.3, 2.06 mg/L)

ABSTRACT: Complex mixtures of persistent organic pollutants (POPs) are regularly detected in the environment and animal tissues. Often these chemicals are associated with latent effects following early-life exposures, following the developmental origin of health and disease paradigm. We investigated the long-term effects of a human relevant mixture of 29 POPs on adult zebrafish following a developmental exposure, in addition to a single PFOS exposure for comparison, as it was the compound with the highest concentration within the mixture. Zebrafish embryos were exposed from 6 to 96 hours post fertilization to x10 and x70 the level of POP mixture or PFOS found in human blood before being transferred to clean water. We measured growth, swimming performance, and reproductive output at different life stages. In addition, we assessed anxiety behavior of the adults and their offspring, as well as performing a transcriptomic analysis on the adult zebrafish brain, as the POP mixture and PFOS concentrations used are known to affect larval behavior. Exposure to POP mixture and PFOS reduced swimming performance and increased length and weight, compared to controls. No effect of developmental exposure was observed on reproductive output or anxiety behavior. Additionally, RNA-seq did not reveal pathways related to anxiety although pathways related to synapse biology were affected at the x10 PFOS level. Furthermore, pathway analysis of the brain transcriptome of adults exposed as larvae to the low concentration of PFOS revealed enrichment in pathways such as calcium, MAPK, and GABA signaling, all of which are important for learning and memory. Based on our results we can conclude that some effects on the endpoints measured were apparent, but if these effects lead to adversities at population levels remains elusive.

ORGANISM(S): Danio rerio

PROVIDER: GSE162503 | GEO | 2020/12/03

REPOSITORIES: GEO

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Project description:Background: Exposure to persistent organic pollutants (POPs) and disruptions in the gastrointestinal microbiota have been positively correlated with a predisposition to factors such as obesity, metabolic syndrome, and type 2 diabetes; however, it is unclear how the microbiome contributes to this relationship. Objective: This study aimed to explore the association between early-life exposure to a potent aryl hydrocarbon receptor (AHR) agonist and persistent disruptions in the microbiota, leading to impaired metabolic homeostasis later in life. Methods: This study utilized metagenomics, NMR- and mass spectrometry-based metabolomics, and biochemical assays to analyze the gut microbiome composition and function, as well as the physiological and metabolic effects of early-life exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF) in conventional, germ-free (GF), and Ahr-null mice. The impact of TCDF on Akkermansia muciniphila (A. muciniphila) in vitro was assessed using optical density (OD 600), flow cytometry, transcriptomics, and mass spectrometry-based metabolomics. Results: TCDF-exposed mice exhibited disruption in the gut microbiome community structure and function, characterized by lower abundances of A. muciniphila, lower levels of cecal short chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), and a reduction in gut hormones GLP-1 and PYY. Importantly, microbial and metabolic phenotypes associated with early-life POP exposure were transferable to GF recipients in the absence of POP carry-over. In addition, AHR-independent interactions between POPs and the microbiota were observed, significantly affected the growth, physiology, gene expression, and metabolic activity of A. muciniphila, resulting in suppressed activity along the ILA pathway. Conclusions: These data point to the complex effects of POPs on the host and microbiota, providing strong evidence that early-life, short-term, and self-limiting POP exposure can adversely impact the microbiome, persisting into later life with associated health implications.

Dataset Information

Transcriptomic analysis of adult zebrafish brain exposed developmentally to 2 concentrations of a persistent organic pollutants (POP) mixture or 2 concentrations of PFOS (0.3, 2.06 mg/L)

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