Exposure of pregnant mice to carbon black by intratracheal instillation

Toxicogenomic effects in dams and offspring

Petra Jackson, Karin Hougaard, Ulla Vogel, Dongmei Wu, Lorraine Casavant, Andrew Williams, Mike Wade, Carole L. Yauk, Håkan Wallin, Sabina Halappanavar

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Exposure to nanomaterials (NM) during sensitive developmental stages 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 response, such as inflammation during gestation, leads to secondary effects in the fetus. Time-mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Nanopure water) or one of three concentrations (2.75, 13.5 or 67 μg in 40 μl Nanopure water) of carbon black Printex 90 (CB) on gestational days 7, 10, 15 and 18, to final cumulative doses of 11, 54 or 268 μg/animal. Samples from a subset of male and female newborns were collected on postnatal day 2 (4 days after the last maternal exposure) and from dams 26 to 27 days post-exposure (post-weaning period). 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 pregnancy. Hepatic gene expression in newborns was interpreted in light of the observed biological responses and gene expression changes arising in the lungs of dams following CB exposure. Although retention of CB particles was observed in dams from both the medium and the high dose groups, neutrophil-marked inflammation and altered expression of several cytokines and chemokines, both at the transcriptional and tissue protein levels, was significant only in the high dose group. Analysis of newborn livers by DNA microarrays revealed that female offspring were more sensitive to maternal exposure than male offspring. Cellular signalling, inflammation, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males, however, responded with subtle changes in metabolism-related genes. Further investigation is required to determine the long-term health consequences of the gene expression changes in offspring and response to environmental stresses.
    OriginalsprogEngelsk
    TidsskriftMutation Research - Genetic Toxicology and Environmental Mutagenesis
    Vol/bind745
    Udgave nummer1-2
    Sider (fra-til)73-83
    ISSN1383-5718
    DOI
    StatusUdgivet - 2012

    Citer dette

    Jackson, Petra ; Hougaard, Karin ; Vogel, Ulla ; Wu, Dongmei ; Casavant, Lorraine ; Williams, Andrew ; Wade, Mike ; Yauk, Carole L. ; Wallin, Håkan ; Halappanavar, Sabina . / Exposure of pregnant mice to carbon black by intratracheal instillation : Toxicogenomic effects in dams and offspring. I: Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2012 ; Bind 745, Nr. 1-2. s. 73-83.
    @article{9b384a5380a641b683f369b7a499cd1e,
    title = "Exposure of pregnant mice to carbon black by intratracheal instillation: Toxicogenomic effects in dams and offspring",
    abstract = "Exposure to nanomaterials (NM) during sensitive developmental stages 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 response, such as inflammation during gestation, leads to secondary effects in the fetus. Time-mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Nanopure water) or one of three concentrations (2.75, 13.5 or 67 μg in 40 μl Nanopure water) of carbon black Printex 90 (CB) on gestational days 7, 10, 15 and 18, to final cumulative doses of 11, 54 or 268 μg/animal. Samples from a subset of male and female newborns were collected on postnatal day 2 (4 days after the last maternal exposure) and from dams 26 to 27 days post-exposure (post-weaning period). 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 pregnancy. Hepatic gene expression in newborns was interpreted in light of the observed biological responses and gene expression changes arising in the lungs of dams following CB exposure. Although retention of CB particles was observed in dams from both the medium and the high dose groups, neutrophil-marked inflammation and altered expression of several cytokines and chemokines, both at the transcriptional and tissue protein levels, was significant only in the high dose group. Analysis of newborn livers by DNA microarrays revealed that female offspring were more sensitive to maternal exposure than male offspring. Cellular signalling, inflammation, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males, however, responded with subtle changes in metabolism-related genes. Further investigation is required to determine the long-term health consequences of the gene expression changes in offspring and response to environmental stresses.",
    author = "Petra Jackson and Karin Hougaard and Ulla Vogel and Dongmei Wu and Lorraine Casavant and Andrew Williams and Mike Wade and Yauk, {Carole L.} and H{\aa}kan Wallin and Sabina Halappanavar",
    year = "2012",
    doi = "10.1016/j.mrgentox.2011.09.018",
    language = "English",
    volume = "745",
    pages = "73--83",
    journal = "Mutation Research - Genetic Toxicology and Environmental Mutagenesis",
    issn = "1383-5718",
    publisher = "Elsevier BV",
    number = "1-2",

    }

    Jackson, P, Hougaard, K, Vogel, U, Wu, D, Casavant, L, Williams, A, Wade, M, Yauk, CL, Wallin, H & Halappanavar, S 2012, 'Exposure of pregnant mice to carbon black by intratracheal instillation: Toxicogenomic effects in dams and offspring', Mutation Research - Genetic Toxicology and Environmental Mutagenesis, bind 745, nr. 1-2, s. 73-83. https://doi.org/10.1016/j.mrgentox.2011.09.018

    Exposure of pregnant mice to carbon black by intratracheal instillation : Toxicogenomic effects in dams and offspring. / Jackson, Petra; Hougaard, Karin; Vogel, Ulla; Wu, Dongmei; Casavant, Lorraine; Williams, Andrew; Wade, Mike; Yauk, Carole L.; Wallin, Håkan; Halappanavar, Sabina .

    I: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Bind 745, Nr. 1-2, 2012, s. 73-83.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Exposure of pregnant mice to carbon black by intratracheal instillation

    T2 - Toxicogenomic effects in dams and offspring

    AU - Jackson, Petra

    AU - Hougaard, Karin

    AU - Vogel, Ulla

    AU - Wu, Dongmei

    AU - Casavant, Lorraine

    AU - Williams, Andrew

    AU - Wade, Mike

    AU - Yauk, Carole L.

    AU - Wallin, Håkan

    AU - Halappanavar, Sabina

    PY - 2012

    Y1 - 2012

    N2 - Exposure to nanomaterials (NM) during sensitive developmental stages 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 response, such as inflammation during gestation, leads to secondary effects in the fetus. Time-mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Nanopure water) or one of three concentrations (2.75, 13.5 or 67 μg in 40 μl Nanopure water) of carbon black Printex 90 (CB) on gestational days 7, 10, 15 and 18, to final cumulative doses of 11, 54 or 268 μg/animal. Samples from a subset of male and female newborns were collected on postnatal day 2 (4 days after the last maternal exposure) and from dams 26 to 27 days post-exposure (post-weaning period). 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 pregnancy. Hepatic gene expression in newborns was interpreted in light of the observed biological responses and gene expression changes arising in the lungs of dams following CB exposure. Although retention of CB particles was observed in dams from both the medium and the high dose groups, neutrophil-marked inflammation and altered expression of several cytokines and chemokines, both at the transcriptional and tissue protein levels, was significant only in the high dose group. Analysis of newborn livers by DNA microarrays revealed that female offspring were more sensitive to maternal exposure than male offspring. Cellular signalling, inflammation, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males, however, responded with subtle changes in metabolism-related genes. Further investigation is required to determine the long-term health consequences of the gene expression changes in offspring and response to environmental stresses.

    AB - Exposure to nanomaterials (NM) during sensitive developmental stages 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 response, such as inflammation during gestation, leads to secondary effects in the fetus. Time-mated C57BL/6BomTac mice were exposed by intratracheal instillation to vehicle (Nanopure water) or one of three concentrations (2.75, 13.5 or 67 μg in 40 μl Nanopure water) of carbon black Printex 90 (CB) on gestational days 7, 10, 15 and 18, to final cumulative doses of 11, 54 or 268 μg/animal. Samples from a subset of male and female newborns were collected on postnatal day 2 (4 days after the last maternal exposure) and from dams 26 to 27 days post-exposure (post-weaning period). 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 pregnancy. Hepatic gene expression in newborns was interpreted in light of the observed biological responses and gene expression changes arising in the lungs of dams following CB exposure. Although retention of CB particles was observed in dams from both the medium and the high dose groups, neutrophil-marked inflammation and altered expression of several cytokines and chemokines, both at the transcriptional and tissue protein levels, was significant only in the high dose group. Analysis of newborn livers by DNA microarrays revealed that female offspring were more sensitive to maternal exposure than male offspring. Cellular signalling, inflammation, cell cycle and lipid metabolism were among the biological pathways affected in female offspring. Males, however, responded with subtle changes in metabolism-related genes. Further investigation is required to determine the long-term health consequences of the gene expression changes in offspring and response to environmental stresses.

    U2 - 10.1016/j.mrgentox.2011.09.018

    DO - 10.1016/j.mrgentox.2011.09.018

    M3 - Journal article

    VL - 745

    SP - 73

    EP - 83

    JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

    JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis

    SN - 1383-5718

    IS - 1-2

    ER -