The mammalian germline corrects deleterious effects of endocrine disruptors
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE59543 | GEO | 2015/02/18
SECONDARY ACCESSION(S): PRJNA255525
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-02-18 | E-GEOD-59543 | biostudies-arrayexpress
Project description:The mammalian germline corrects deleterious effects of endocrine disruptors
| PRJNA255525 | ENA
Project description:Exposure to environmental endocrine-disrupting chemicals during pregnancy reportedly causes transgenerationally inherited reproductive defects. We hypothesized that to affect the grandchild, endocrine-disrupting chemicals must alter the epigenome of the germ cells of the in utero-exposed G1 male fetus. Additionally, to affect the great-grandchild, the aberration must persist in the germ cells of the unexposed G2 grandchild.Here, we treat gestating female mice with vinclozolin, bisphenol A, or di-(2-ethylhexyl)phthalate during the time when global de novo DNA methylation and imprint establishment occurs in the germ cells of the G1 male fetus. We map genome-wide features in purified G1 and G2 prospermatogonia, in order to detect immediate and persistent epigenetic aberrations, respectively. We detect changes in transcription and methylation in the G1 germline immediately after endocrine-disrupting chemicals exposure, but changes do not persist into the G2 germline. Additional analysis of genomic imprints shows no persistent aberrations in DNA methylation at the differentially methylated regions of imprinted genes between the G1 and G2 prospermatogonia, or in the allele-specific transcription of imprinted genes between the G2 and G3 soma.Our results suggest that endocrine-disrupting chemicals exert direct epigenetic effects in exposed fetal germ cells, which are corrected by reprogramming events in the next generation. Avoiding transgenerational inheritance of environmentally-caused epigenetic aberrations may have played an evolutionary role in the development of dual waves of global epigenome reprogramming in mammals.
| S-EPMC4376074 | biostudies-other
Project description:The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable endocrine disruption (ED) assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17a-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos.
2014-03-06 | GSE44263 | GEO
Project description:Anthropogenic contaminants in water can impose risks to reproductive health. Most of these compounds are known to be endocrine disrupting chemicals (EDCs). EDCs can impact the endocrine system and subsequently impair the development and fertility of non-human animals and humans. The source of chemical contamination in water is diverse, originating from byproducts formed during water disinfection processes, release from industry and livestock activity, or therapeutic drugs released into sewage. This review discusses the occurrence of EDCs in water such as disinfection byproducts, fluorinated compounds, bisphenol A, phthalates, pesticides, and estrogens, and it outlines their adverse reproductive effects in non-human animals and humans.
| S-EPMC7139484 | biostudies-literature
Project description:BackgroundWhen a biologic mechanism of interest is anticipated to operate differentially according to sex, as is often the case in endocrine disruptors research, investigators routinely estimate sex-specific associations. Less attention has been given to potential sexual heterogeneity of confounder associations with outcomes. When relationships of covariates with outcomes differ according to sex, commonly applied statistical approaches for estimating sex-specific endocrine disruptor effects may produce divergent estimates.ObjectivesWe discuss underlying assumptions and evaluate the performance of two traditional approaches for estimating sex-specific effects, stratification and product terms, and introduce a simple modeling alternative: an augmented product term approach.MethodsWe describe the impact of assumptions regarding sexual heterogeneity of confounder relationships on estimates of sex-specific effects of the exposure of interest for three approaches: stratification, traditional product terms, and augmented product terms. Using simulated and applied examples, we demonstrate properties of each approach under a range of scenarios.ResultsIn simulations, sex-specific exposure effects estimated using the traditional product term approach were biased when confounders had sex-dependent associations with the outcome. Sex-specific estimates from stratification and the augmented product term approach were unbiased but less precise. In the applied example, the three approaches yielded similar estimates, but resulted in some meaningful differences in conclusions based on statistical significance.ConclusionsInvestigators should consider sexual heterogeneity of confounder associations when choosing an analytic approach to estimate sex-specific effects of endocrine disruptors on health. In the presence of sex-dependent confounding, our augmented product term approach may be advantageous over stratification when there is prior knowledge available to fit reduced models or when investigators seek an automated test for effect measure modification. https://doi.org/10.1289/EHP334.
| S-EPMC5743445 | biostudies-literature
Project description:The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable endocrine disruption (ED) assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17a-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos. Newly fertilized embryos (<2hpf) were exposed for 48 hours to 0.65mg/l (EC10) and 0.8mg/l (EC20) 17-alpha ethinylestradiol (EE2), 1.2mg/l (EC10) and 1.4mg/l (EC20) flutamide, 8 mg/l (EC10)and 8.5mg/l (EC20) bisphenol A(BPA), 0.8 mg/l (EC10) and 1.1mg/l (EC20) propanil, 19.8mg/l (EC10) and 24.4mg/l (EC20) methylparaben, 1.2 mg/l (EC10) and 1.3mg/l (EC20) linuron as well as to 1.7mg/l (EC10) and 2 mg/l (EC20) prochloraz. Water controls were included in all studies and acetone solvent controls were applied when indicated (AC). For each study, four replicates (a,b,c,d) were performed per condition, each consisting of 24 pooled embryos.
2014-03-06 | E-GEOD-44263 | biostudies-arrayexpress
Project description:Environmental endocrine disruptors (EDs) are synthetic chemicals that resemble natural hormones and are known to cause epigenetic perturbations. EDs have profound effects on development and fertility. Imprinted genes had been identified as susceptible loci to environmental insults by EDs because they are functionally haploid, and because the imprints undergo epigenetic resetting between generations. To screen for possible epigenetic perturbations caused by EDs at imprinted loci, we treated pregnant mice daily between 8.5 and 12.5 days post coitum (dpc) with di-(2-ethylhexyl)-phthalate (DEHP), bisphenol A (BPA), vinclozolin (VZ), or control oil vehicle. After isolating RNA from the placenta, yolk sac, amnion, head, body, heart, liver, lung, stomach, and intestines of 13.5 dpc embryos we measured the allele-specific expression of 38 imprinted transcripts using multiplex single nucleotide primer extension (SNuPE) assays. In this representative data set we identified only a small number of transcripts that exhibited a substantial relaxation of imprinted expression with statistical significance: Slc22a18 with 10% relaxation in the embryo after BPA treatment; Rtl1as with 11 and 16% relaxation in the lung and placenta, respectively after BPA treatment; and Rtl1 with 12% relaxation in the yolk sac after DEHP treatment. Additionally, the standard deviation of allele-specificity increased in various organs after ED treatment for several transcripts including Igf2r, Rasgrf1, Usp29, Slc38a4, and Xist. Our data suggest that the maintenance of strongly biased monoallelic expression of imprinted genes is generally insensitive to EDs in the 13.5 dpc embryo and extra-embryonic organs, but is not immune to those effects.
| S-EPMC3154434 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-03-11 | GSE130436 | GEO
Project description:BackgroundProstaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine-disrupting compounds (EDCs) share a high degree of structural similarity with mild analgesics.Objectives and methodsUsing cell-based transfection and transduction experiments, mass spectrometry, and organotypic assays together with molecular modeling, we investigated whether inhibition of the PG pathway by known EDCs could be a novel point of endocrine disruption.ResultsWe found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis, and this reduction was correlated with a reduced testosterone production. The inhibition of PG synthesis occurred without involvement of canonical PG receptors or the peroxisome proliferator-activated receptors (PPARs), which have previously been described as targets of EDCs. Instead, our results suggest that the compounds may bind directly into the active site of the cyclooxygenase (COX) enzymes, thereby obstructing the conversion of arachidonic acid to PG precursors without interfering with the expression of the COX enzymes. A common feature of the PG inhibitory EDCs is the presence of aromatic groups that may stabilize binding in the hydrophobic active site of the COX enzymes.ConclusionOur findings suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades.
| S-EPMC3080937 | biostudies-literature