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The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine [ChIP-Seq]

ABSTRACT: Environmental factors such as pesticides are widely used in the agriculture of many countries and their negative impact on human health and fertility are largely unknown. There is a rapidly growing body of evidence that human reproductive health is negatively affected by various environmental factors, including life style and exposure to chemical compounds such as certain drugs and pesticides. Sexually reproducing organisms produce haploid gametes via a process called meiosis. Meiosis is dependent on androgen action within the testis. Pesticides and herbicides interfere with natural hormones system and are considered to be endocrine disruptors. We hypothesize that atrazine (ATZ), a herbicide used globally, adversely affects meiosis. To test this idea we used the mouse as a model organism. Mice were treated for a three weeks with atrazine at a concentration of 100 mg/l in drinking water nearly corresponding to 25mg/kg/day. To access the extent of the toxic effect of atrazine on the epigenetic modifications on genome wide level we performed Chromatin immunoprecipitation (ChIP) using antibody against H3K4me3 followed by high throughput sequencing. Analysis of H3K4me3 marks revealed that 823 genomic loci were affected. H3K4me3 marks are increased occupancy in highly overexpressed Speer and Trim45 genes and decreased in Entd4, Slc25a37 and LoxL2 genes. Changes in H3K4me3 occupancy in these genes may reflect answers to DNA damages in ATZ treated testis tissue. Eighty seven of differential H3K4me3 peaks are associated with meiosis specific Double Strand Breaks (DSB) sites, showing that ATZ treatment affect DSBs repair in meiosis. Together, our data demonstrate the negative effect of atrazine on meiosis in mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE64035 | GEO | 2015/10/01

SECONDARY ACCESSION(S): PRJNA269925

REPOSITORIES: GEO

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Project description:Atrazine (ATZ) and nonylphenol (NP) are commonly identified contaminants in aquatic habitats; however, relatively few studies have considered the impact of these endocrine disrupters on immune function. This study examined the immunotoxicological effects of ATZ and NP at multiple levels of biological organization. Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to a solvent control (0.00625 % v/v anhydrous ethanol), 59 µg/L ATZ, 555 µg/L ATZ, 2.3 µg/L NP or 18 µg/L NP (measured concentrations) for 4 d. At the end of exposure, fish were assessed for general health indicators (liver somatic index (LSI), spleen somatic index (SSI), hematocrit), biochemical endpoints (plasma cortisol concentrations, lysozyme activity, and protein content), a cellular endpoint (blood leukocyte differential counts), and an integrated immune response at the organism level (host resistance challenge with Listonella anguillarum). Additionally, liver gene expression was assessed using a salmonid microarray (cGRASP, 32K version 1) for fish exposed to the (solvent) control, high ATZ (555 µg/L) and high NP (18 µg/L) treatments. Fish exposed to the high ATZ concentration exhibited elevated plasma cortisol, a decrease in SSI, and decreased lymphocytes and increased monocytes in peripheral blood, with suppression of early immune system processes apparent at the molecular level. In contrast, fish exposed to the high NP concentration showed physiological (e.g. elevated LSI) and gene expression changes (e.g. induction of vitellogenin) consistent with estrogenic effects, as well as decreased lymphocytes in the peripheral blood and more limited alteration in immune system related pathways in the liver transcriptome. Fish exposed to high ATZ or NP concentrations suffered higher mortality than the control group following disease challenge with L. anguillarum. Microarray analysis of the liver transcriptome revealed a total of 211 unique, annotated differentially-regulated genes (DRGs) following high ATZ exposure and 294 DRGs following high NP exposure, with signatures that included alterations to a number of immune-system related processes and pathways. Functional (enrichment) analysis revealed effects on immune system function, metabolism, oxygen homeostasis, cell cycle, DNA damage, and other processes affected by ATZ or NP exposure. Overall this study provides evidence at multiple levels of biological organization that both ATZ and NP are immunotoxic and highlights the potential risk posed by these chemicals to wild fish populations. Total of 24 microarrays. 1 experimental sample and 1 pooled reference sample per microarray. Total of 8 individual samples (replicates) per treatment group. Three (3) treatment groups: control, atrazine (ATZ, 555 ug/L) and nonylphenol (NP, 18 ug/L).

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The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine [ChIP-Seq]

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