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Exposure of pregnant mice to carbon black by intratracheal instillation: toxicogenomics effects in dams and offspring

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE29764 | GEO | 2012/04/02

SECONDARY ACCESSION(S): PRJNA141029

REPOSITORIES: GEO

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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.

Project description:In the present study we investigate the effect of maternal pulmonary exposure to titanium dioxide (UV-Titan designed for use in the paint and lacquer industry) on prenatally exposed offspring. Time-mated mice (C57BL/6BomTac) were exposed by inhalation for 1 h/day to 42 mg UV-titan/m3 aerosolized powder or filtered air during gestation days (GD) 8-18. We evaluated levels of DNA strand breaks using the comet assay in bronchioalveolar lavage (BAL) cells and liver cells of the time-mated mice, and in liver cells of the offspring. In parallel, we analyzed changes in gene expression in the liver tissue of offspring using DNA microarrays. We demonstrate that UV-Titan did not induce DNA strand breaks in the time-mated mice or their offspring. Transcriptional profiling of newborn liver tissue revealed changes in the expression of genes related to the retinoic acid (RA) signalling pathway in the females, while gene expression in male offspring was relatively unaffected by exposure. Time-mated, nulliparous mice (C57BL/6BomTac, Taconic Europe, Ejby, Denmark) were exposed to filtered clean air or approximately 42 mg/m3 UV-Titan on GD 8M-bM-^@M-^S18 for 1 hr/day by a whole-body exposure.Delivery was expected on GD 20, and designated postnatal day (PND) 0. On PND 2, one offspring (M-bM-^@M-^\newbornM-bM-^@M-^]) per litter was killed by decapitation, to yield litters with at least 5 offspring per exposure group. The newborn offspring were collected two days after birth. On PND 23-24 (M-bM-^@M-^\at weaningM-bM-^@M-^]) one male and one female per litter were killed. Organs were dissected, weighed, placed in NUNC cryotubes, snap frozen in liquid N2 and stored at -80M-BM-0C until analysis. Exposed dams were killed on PND 24-25 (26-27 days after last exposure). DNA strad break detection was carried out in bronchoalveolar lavage fluid in dams by COMET assay. Total RNA was extracted from offspring livers and gene expression profiling was carried out on whole liver tissues from offspring. 9 UV-Titan treated and 7 controls mice consisting of 8 males and 8 females mRNA, hepatic, developmental, Toxicogenomics, nano-titanium dioxide

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Exposure of pregnant mice to carbon black by intratracheal instillation: toxicogenomics effects in dams and offspring

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