Toxicokinetics and Metabolomic Disrupting of the Flame Retardant Mixture Firemaster 550
Ontology highlight
ABSTRACT:
ORGANISM(S): Rat Rattus Norvegicus
TISSUE(S): Placenta
SUBMITTER: 
Susan Sumner
PROVIDER: ST000415 | MetabolomicsWorkbench | Thu Jun 16 00:00:00 BST 2016
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description:Provided later Pregnant Fisher 344 rats will be purchased from Charles River Laboratories, Inc. and delivered to CIIT on gestational day (GD) 7 (GD0 = day first vaginal plug positive). At gestational day 12 (GD12), the dams will be exposed once/day until GD20 to 50 mg/kg dibutyl phthalate (DBP) in corn oil vehicle via oral gavage. Each dose group will contain 4-6 vehicle control or phthalate treated dams. Groups of animals will be sacrificed at GD20, postnatal day (PND) 35, and PND90 for endpoint analysis. At GD20, treated and control animals will be examined for various endpoints including body weight, testicular histopathology, gene expression profile via microarray analysis, and anogenital distance (AGD). AGD (at parturition; PND1) and nipple number/location (at PND14 and day of sacrifice) will be determined on animals in the postnatal groups. At PND35 or 90, one male from each in utero corn oil vehicle or DBP exposed group will receive a second gavage of either corn oil or 500 mg/kg DBP. 6 hours after the second gavage, the following endpoints will be examined: 1) testis histopathology; 2) spermatid head quantification (PND90 only); 3) testis and body weights; 5) genome-wide gene expression (via microarray); and 6) germ cell apoptosis (TUNEL assay).
2008-11-24 | E-GEOD-13550 | biostudies-arrayexpress
Project description:Environmental estrogens may affect epigenetic programming as early as the period of preimplantation development. Therefore, we analyzed the effects of continuous gestational estradiol-17β (E2) exposure on male and female embryos. A low dose, close to the no-observed effect level (NOEL - 10 µg E2/kg body weight(bw)/d), a high dose (1000 µg E2/kg bw/d) and carrier only, as control group, was fed to sows from insemination until sampling at day 10 of pregnancy, respectively. 36 samples (n = 5-7 per treatment group and sex) were analyzed by high throughput sequencing.In the high dose group, RNA-sequencing of single embryos revealed 982 differentially expressed genes (DEG) in the female but none in the male blastocysts. Moreover, 62 and 3 DEG were found in female and male embryos of the NOEL dose group, respectively. Thus, maternal E2 treatment during early pregnancy affected gene expression of the embryos at day 10, potentially constituting the basis for long-term adverse effects.
2018-10-16 | E-MTAB-6263 | biostudies-arrayexpress
Project description:Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung, and bladder cancers, and cardiovascular disease. The mechanisms behind arsenic's effects remain unclear, but recent research indicates that aresnic acts along sex-specific lines and may be an endocrine disruptor. The objective of this study was to evaluate the nature of gene expression chagnes among males and females exposed to arsenic contaminated water in Bangladesh at high and low dose exposures.The median wAs concentration for the low exposure group was 103 µg/L for males and 117 µg/L for females (range 50–200 µg/L). For the high exposure group, the median wAs concentration was 355 µg /L for males (range 250-500 µg /L) and 434 µg/L for females (range 232–1000 µg /L). The PBMCs of males with high exposure compared to those with low exposure there were 534 differentially expressed genes (p <0.05); and for females with high exposure relative to low exposure there were 645 differentially expressed genes (p <0.05) in PBMCs of females.
2015-06-01 | GSE57711 | GEO
Project description:Exposure to nanomaterials (NM) during sensitive stages of development may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM-induced stress, such as inflammation during gestation, can lead to secondary effects in the growing fetus. Time mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Milli Q water) or one of three concentrations (2.75, 13.5 or 67 µg/animal) of carbon black Printex 90 (CB) dispersions on gestational days 7, 10, 15 and 18 to a total final dose of 11, 54 or 268 µg/animal. Male and female newborns were sacrificed on day 2 after birth (PND2, 4 days after the last maternal exposure) and dams were sacrificed after weaning of offspring (26-27 days post-exposure). Histopathology, DNA microarrays, pathway-specific RT-PCR arrays, focussed RT-PCR, and tissue protein analysis were employed to characterize pulmonary response in dams exposed to CB during gestation. Gene expression profiles in newborn livers were interpreted in light of toxic effects of CB to dams indicated by gene expression profiles of dam lungs. Although retention of CB particles was observed in dams from both medium and high dose groups, neutrophil-marked inflammation was significant only in the high dose group dams. Inflammation in dams was accompanied by altered expression of several cytokines and chemokines both at the transcriptional and tissue protein levels. Analysis of newborn livers by DNA microarrays revealed that female offspring were much more sensitive to maternal stress than males. Cellular signalling, inflammation, immune response, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males however, responded with subtle changes in genes involved in metabolism. At present, the implications of altered biological pathways in offspring in response to in utero exposure to particles are not well understood. Further investigation will be required to determine if there are long term consequences to offspring in terms of health and responses to environmental stresses.
2012-04-02 | GSE29761 | GEO
Project description:Exposure to nanomaterials (NM) during sensitive stages of development may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM-induced stress, such as inflammation during gestation, can lead to secondary effects in the growing fetus. Time mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Milli Q water) or one of three concentrations (2.75, 13.5 or 67 µg/animal) of carbon black Printex 90 (CB) dispersions on gestational days 7, 10, 15 and 18 to a total final dose of 11, 54 or 268 µg/animal. Male and female newborns were sacrificed on day 2 after birth (PND2, 4 days after the last maternal exposure) and dams were sacrificed after weaning of offspring (26-27 days post-exposure). Histopathology, DNA microarrays, pathway-specific RT-PCR arrays, focussed RT-PCR, and tissue protein analysis were employed to characterize pulmonary response in dams exposed to CB during gestation. Gene expression profiles in newborn livers were interpreted in light of toxic effects of CB to dams indicated by gene expression profiles of dam lungs. Although retention of CB particles was observed in dams from both medium and high dose groups, neutrophil-marked inflammation was significant only in the high dose group dams. Inflammation in dams was accompanied by altered expression of several cytokines and chemokines both at the transcriptional and tissue protein levels. Analysis of newborn livers by DNA microarrays revealed that female offspring were much more sensitive to maternal stress than males. Cellular signalling, inflammation, immune response, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males however, responded with subtle changes in genes involved in metabolism. At present, the implications of altered biological pathways in offspring in response to in utero exposure to particles are not well understood. Further investigation will be required to determine if there are long term consequences to offspring in terms of health and responses to environmental stresses.
2012-04-02 | GSE29762 | GEO
Project description:Exposure to nanomaterials (NM) during sensitive stages of development may predispose organisms to diseases later in life. However, direct translocation of NM from mother to fetus through the placenta is limited. The present study tests the hypothesis that pulmonary exposure to NM and NM-induced stress, such as inflammation during gestation, can lead to secondary effects in the growing fetus. Time mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Milli Q water) or one of three concentrations (2.75, 13.5 or 67 µg/animal) of carbon black Printex 90 (CB) dispersions on gestational days 7, 10, 15 and 18 to a total final dose of 11, 54 or 268 µg/animal. Male and female newborns were sacrificed on day 2 after birth (PND2, 4 days after the last maternal exposure) and dams were sacrificed after weaning of offspring (26-27 days post-exposure). Histopathology, DNA microarrays, pathway-specific RT-PCR arrays, focussed RT-PCR, and tissue protein analysis were employed to characterize pulmonary response in dams exposed to CB during gestation. Gene expression profiles in newborn livers were interpreted in light of toxic effects of CB to dams indicated by gene expression profiles of dam lungs. Although retention of CB particles was observed in dams from both medium and high dose groups, neutrophil-marked inflammation was significant only in the high dose group dams. Inflammation in dams was accompanied by altered expression of several cytokines and chemokines both at the transcriptional and tissue protein levels. Analysis of newborn livers by DNA microarrays revealed that female offspring were much more sensitive to maternal stress than males. Cellular signalling, inflammation, immune response, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males however, responded with subtle changes in genes involved in metabolism. At present, the implications of altered biological pathways in offspring in response to in utero exposure to particles are not well understood. Further investigation will be required to determine if there are long term consequences to offspring in terms of health and responses to environmental stresses. This SuperSeries is composed of the SubSeries listed below.
2012-04-02 | GSE29764 | GEO
Project description:The aim of this study was to evaluate the potential effects of methyl donor supplementation of pregnant animals in the presence or absence of a concomitant lactation on the methylome of the offspring. Twenty Holstein cows, 10 nulliparous (not lactating while pregnant) and 10 multiparous (lactating while pregnant) were blocked by parity and randomly assigned to an i.m. weekly injections of a placebo (CTRL) or a solution containing methyl donors (MET). After calving, 5 calves randomly selected from each treatment (two born to primiparous and three to multiparous dams) were blood-sampled to determine their full methylome. There were more than 2,000 CpG differentially methylated between calves born to CTRL and those born to MET, and also between calves born to multiparous and nulliparous dams. Most of the differences affected genes involved in immune function, cell growth regulation and differentiation, kinase activity, and ion channeling. We conclude that the coexistence of pregnancy and lactation affects the methylome of the offspring, and that supplementation of methyl donors early in gestation has also consequences on the methylome.
2017-08-17 | GSE102736 | GEO
Project description:Firemaster® 550 (FM 550) is a flame retardant (FR) mixture that has become one of the most commonly used FRs in foam-based furniture and baby products. Human exposure to this commercial mixture, comprised of brominated and organophosphate components, is widespread. We have repeatedly shown that developmental exposure can lead to sex-specific behavioral effects in rats. Accruing evidence of endocrine disruption and potential neurotoxicity have raised concerns regarding the neurodevelopmental effects of FM 550 exposure, but the specific mechanisms of action remains unclear. Additionally, we observed significant, and in some cases sex-specific, accumulation of FM 550 in placental tissue following gestational exposure. Because the placenta is an important source of hormones and neurotransmitters for the developing brain, it may be a critical target of toxicity to consider in the context of developmental neurotoxicity. Using a mixture of targeted and exploratory approaches, the goal of the present study was to identify possible mechanisms of action in the developing forebrain and placenta. Wistar rat dams were orally exposed to FM 550 (0, 300, or 1,000 µg/day;) for 10 days during gestation and placenta and fetal forebrain tissue collected for analysis. In placenta, evidence of endocrine, inflammatory, and neurotransmitter signaling pathway disruption was identified. Notably, 5-HT turnover was reduced in placental tissue and fetal forebrains indicating that 5-HT signaling between the placenta and the embryonic brain may be disrupted. These findings demonstrate that environmental contaminants, like FM 550, have the potential to impact the developing brain by disrupting normal placental functions.
2018-02-28 | GSE108965 | GEO
Project description:In this dose series pregnant CD-1 (outbred) dams were exposed to the 2-chloro analogue of 2'-deoxyadenosine (a metabolic toxin) on 8 d.p.c. Test doses were developed from a teratological series for 2CdA-induced microphthalmia using BMDS modeling software from the US EPA. Benchmark doses for microarray analysis were: 5.0 mg/kg (25% risk), 2.5 mg/kg (5% risk), 1.25 mg/kg (NOAEL), and 0.625 mg/kg (subNOAEL). All measurements were on RNA from the embryo proper at 3.0h post-treatment. Keywords = dose series Keywords = 2-chloro-2'deoxyadenosine Keywords = embryo Keywords = microphthalmia Keywords: dose response
2004-03-11 | GSE1068 | GEO
Project description:In this dose series pregnant CD-1 (outbred) dams were exposed to methylmercury (MeHg) as monomethylmercuric chloride injected intraperitoneally on 9 d.p.c. Test doses were 10.0 mg/kg and below. This regimen induces symptoms of Fetal Minimata Disease (FMD) in term fetuses. Risks with respect to FMD for the various test doses were 10.0 mg/kg (40% risk), 5.0 mg/kg (20% risk), 2.5 mg/kg (NOAEL), and 1.25 mg/kg (subNOAEL). All measurements were on RNA from the embryonic forebrain (prosencephalon and surrounding tissue) at 3.0h post-treatment. Keywords = dose series Keywords = mercury Keywords = embryo Keywords = Fetal Minamata Disease Keywords: dose response
2004-03-11 | GSE1075 | GEO