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The global tissue-specific RNA transcription dysregulation effects in the third generation after embryonic exposure to the widely used herbicide atrazine are mediated via inherited histone trimethylation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE81093 | GEO | 2016/09/01

SECONDARY ACCESSION(S): PRJNA320477

REPOSITORIES: GEO

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The global tissue-specific RNA transcription dysregulation effects in the third generation after embryonic exposure to the widely used herbicide atrazine are mediated via inherited histone trimethylation [RNA-Seq]

Project description:We report the effect of histone trimethylation on transgenerational inheritance. We exposed outbred pregnant CD1 mice to herbicide atrazine and progeny of these mice were crossed for a three generations. First (F1) and third (F3) generation of males were analyzed by using genome-wide sequencing analysis. We analyzed the RNA expression level in liver, brain (hypothalamus) and testis in F3 generation males. The testis samples of F1 and F3 generations’ males were analyzed by ChIP-seq using antibody against H3K4me3. We find that subset of H3K4me3 marks altered in F1 was also detected in F3 males progeny. This subset is enriched in genes of stem cell differentiation. We found that embryonic exposure to atrazine globally affects the RNA transcription in testis: we found the tissue-specific transcription deregulation, increased number transcripts with altered transcription start site, alternatively spliced and polyadenylated mRNA transcripts in a F3 generation males. This study provides a new knowledge of mechanisms of transgenerational inheritance exposed to toxic compounds.

2016-09-01 | GSE81091 | GEO

2016-09-01 | GSE81056 | GEO

2016-09-01 | GSE84978 | GEO

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice.

Project description:The epigenetic events imposed during germline reprogramming and affected by harmful exposure can be inherited and transferred to subsequent generations via gametes inheritance. In this study, we examine the transgenerational effects promoted by widely used herbicide atrazine (ATZ). We exposed pregnant outbred CD1 female mice and the male progeny was crossed for three generations with untreated females. We demonstrate here that exposure to ATZ affects meiosis, spermiogenesis and reduces the spermatozoa number in the third generation (F3) male mice. We suggest that changes in testis cell types originate from modified transcriptional network in undifferentiated spermatogonia. Importantly, exposure to ATZ dramatically increases the number of transcripts with novel transcription initiation sites, spliced variants and alternative polyadenylation sites. We found the global decrease in H3K4me3 occupancy in the third generation males. The regions with altered H3K4me3 occupancy in F3 ATZ-derived males correspond to altered H3K4me3 occupancy of F1 generation and 74% of changed peaks in F3 generation are associated with enhancers. The regions with altered H3K4me3 occupancy are enriched in SP family and WT1 transcription factor binding sites. Our data suggest that the embryonic exposure to ATZ affects the development and the changes induced by ATZ are transferred up to three generations.

| S-EPMC5175363 | biostudies-literature

Embryonic exposure to the widely-used herbicide atrazine disrupts meiosis and normal follicle formation in female mice.

Project description:The widely-used herbicide atrazine (ATZ) is detected in ground and surface water in many countries. Several studies in animals have demonstrated that ATZ has endocrine-disrupting effects on male and female reproduction in many vertebrate species. In this study, we investigated the effects of ATZ exposure on meiosis, a key step in gametogenesis in mammals. The treatment was initiated before oocyte entry into meiosis, which occurs during the embryonic period in females. We found that embryonic exposure to ATZ increases the level of 8-oxo-guanine in the nucleus of meiotic cells, reflecting oxidative stress and affecting meiotic double-strand break repair, chromosome synapsis and crossover numbers. Finally, embryonic exposure to ATZ reduces the number of primordial follicles and increases the incidence of multi-oocyte follicles in adult mice. Our data demonstrate that embryonic exposure to ATZ disrupts prophase I of meiosis and affects normal follicle formation in female mice.

| S-EPMC5471253 | biostudies-literature

Project description:The global tissue-specific RNA transcription dysregulation effects in the third generation after embryonic exposure to the widely used herbicide atrazine are mediated via inherited histone trimethylation

| PRJNA320477 | ENA

The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine.

Project description:BackgroundEnvironmental factors such as pesticides can cause phenotypic changes in various organisms, including mammals. We studied the effects of the widely used herbicide atrazine (ATZ) on meiosis, a key step of gametogenesis, in male mice.MethodsGene expression pattern was analysed by Gene-Chip array. Genome-wide mapping of H3K4me3 marks distribution was done by ChIP-sequencing of testis tissue using Illumina technologies. RT-qPCR was used to validate differentially expressed genes or differential peaks.ResultsWe demonstrate that exposure to ATZ reduces testosterone levels and the number of spermatozoa in the epididymis and delays meiosis. Using Gene-Chip and ChIP-Seq analysis of H3K4me3 marks, we found that a broad range of cellular functions, including GTPase activity, mitochondrial function and steroid-hormone metabolism, are affected by ATZ. Furthermore, treated mice display enriched histone H3K4me3 marks in regions of strong recombination (double-strand break sites), within very large genes and reduced marks in the pseudoautosomal region of X chromosome.ConclusionsOur data demonstrate that atrazine exposure interferes with normal meiosis, which affects spermatozoa production.

| S-EPMC4628360 | biostudies-literature

The epigenetic processes of meiosis in male mice are broadly affected by the widely used herbicide atrazine

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-10-01 | GSE64037 | GEO

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

Project description: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 the various environmental factors, including life style and exposure to the 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 three weeks with atrazine in drinking water at concentration of 100 mg/l. To assess the molecular mechanisms of effects of ATZ on spermatogenesis we performed comparative analysis of genes expression by using Affymetrix microarray by using three biological testis samples from ATZ treated and control mice. Using a fold-change cutoff value of 1.5 and p value <0.05 (statistical Limma test (linear models test for microarray data)), we identified 51 genes that were differentially expressed in ATZ treated mice.

2015-10-01 | GSE63983 | GEO

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

Project description: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.

2015-10-01 | GSE64035 | GEO

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