Epigenetic Transgenerational Modifications Induced by Xenobiotic Exposure in Zebrafish

Abstract

Zebrafish (Danio rerio) is a well-established vertebrate model in ecotoxicology research that responds to a wide range of xenobiotics such as pesticides, drugs, and endocrine-disrupting compounds. The epigenome can interact with the environment and transform internal and/or external signals into phenotypic responses through changes in gene transcription. Environmental exposures can also generate epigenetic variations in offspring even by indirect exposure. In this review, we address the advantages of using zebrafish as an experimental animal model to study transgenerational epigenetic processes upon exposure to xenobiotics. We focused mostly on DNA methylation, although studies on post-translational modifications of histones, and non-coding RNAs related to xenobiotic exposure in zebrafish are also discussed. A revision of the methods used to study epigenetic changes in zebrafish revealed the relevance and reproducibility for epigenetics-related research. PubMed and Google Scholar databases were consulted for original research articles published from 2013 to date, by using six keywords: zebrafish, epigenetics, exposure, parental, transgenerational, and F2. From 499 articles identified, 92 were considered, of which 14 were selected as included F2 and epigenetic mechanisms. Current knowledge regarding the effect of xenobiotics on DNA methylation, histone modifications, and changes in non-coding RNAs expressed in F2 is summarized, along with key experimental design considerations to characterize transgenerational effects.

Maternal or Paternal Antibiotics? Intergenerational Transmission and Reproductive Toxicity in Zebrafish

“…In F2 eggs following F0 parental exposure, there was an increased incidence in embryonic death and decreased motility in larvae, even though antibiotic concentrations were below the LOD. These findings suggest that the toxic effect may last longer than the concentration of antibiotics during intergenerational transmission and that the adverse impacts of antibiotics may be currently underestimated. , Meanwhile, the impacts to F2 offspring also suggest that the toxicity might not be directly induced by the occurrence of antibiotics, possibly transmitting the effects through the F1 generation, which is in accordance with previous studies. − Particularly, our previous results provide evidence that, following parental fish exposure, CTC was not detected in F2 eggs but still exhibited adverse effects to macrophages, neutrophils, the expression of immune-related genes, and NF-κB-dependent signaling in the F2 generation . This might be attributed to epigenetic alterations, as previous research suggested that, at low concentration levels, the antibiotic CIP could upregulate apoptotic-related genes and induce histological alterations and genotoxicity in zebrafish …”

Lifelong molecular consequences of high Glucocorticoids exposure during development

“…Since the majority of dGC-primed genes defined here (1657 genes) are differentially regulated in bPAC+ compared to both wild type and bPAC- (S. Fig. 6a) and previously published reports described transgenerational effects on DNA methylation in zebrafish 33,34 , we carried out a comparison of bPAC+ with wildtype brain to identify differentially methylated CpG sites (DMCs). 17.9% of dGC-primed genes (297/1657 genes) exhibited significant DMCs within their promoter and/or gene body regions (Fig.…”

Evaluation of GSTP1, GSTA4 and AChE Gene Methylation in Bovine Lymphocytes Cultured In Vitro with Miconazole Alone and in Combination with Mospilan 20SP

“…Marçal et al [ 21 ] found that the herbicide penoxsulam did not induce global DNA methylation changes in the F 0 generation of crayfish Procambarus clarkii but did find hypomethylation in unexposed F1 crayfish, indicating that events occurring in previous generations might have an impact on subsequent ones. Terrazas-Salgado et al [ 22 ] reviewed studies using zebrafish as an animal model to study the effect of xenobiotics, such as pesticides, drugs, or endocrine disruptors, on transgenerational epigenetic processes, particularly global or gene-specific DNA methylation, e.g., the methylation of FOXA2 (forkhead box protein A2) or rRNA genes. Recent studies using laboratory animal models to investigate the effects of environmental toxicants, including pesticides, on the reproductive system transmitted through generations and underlying epigenetic mechanisms, including DNA methylation, were reviewed by Rebuzzini et al [ 23 ].…”