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  1. Article ; Online: Exposure to a human relevant mixture of persistent organic pollutants or to perfluorooctane sulfonic acid alone dysregulates the developing cerebellum of chicken embryo

    Ajay Yadav / Steven Verhaegen / Panagiotis Filis / Diana Domanska / Robert Lyle / Arvind Y.M. Sundaram / Magnus Leithaug / Gunn Charlotte Østby / Mona Aleksandersen / Hanne Friis Berntsen / Karin Elisabeth Zimmer / Paul A. Fowler / Ragnhild Elisabeth Paulsen / Erik Ropstad

    Environment International, Vol 166, Iss , Pp 107379- (2022)

    2022  

    Abstract: Prenatal exposure to persistent organic pollutants (POPs) is associated with neurodevelopmental disorders. In the present study, we explored whether a human-relevant POP mixture affects the development of chicken embryo cerebellum. We used a defined ... ...

    Abstract Prenatal exposure to persistent organic pollutants (POPs) is associated with neurodevelopmental disorders. In the present study, we explored whether a human-relevant POP mixture affects the development of chicken embryo cerebellum. We used a defined mixture of 29 POPs, with chemical composition and concentrations based on blood levels in the Scandinavian population. We also evaluated exposure to a prominent compound in the mixture, perfluorooctane sulfonic acid (PFOS), alone. Embryos (n = 7–9 per exposure group) were exposed by injection directly into the allantois at embryonic day 13 (E13). Cerebella were isolated at E17 and subjected to morphological, RNA-seq and shot-gun proteomics analyses. There was a reduction in thickness of the molecular layer of cerebellar cortex in both exposure scenarios. Exposure to the POP mixture significantly affected expression of 65 of 13,800 transcripts, and 43 of 2,568 proteins, when compared to solvent control. PFOS alone affected expression of 80 of 13,859 transcripts, and 69 of 2,555 proteins. Twenty-five genes and 15 proteins were common for both exposure groups. These findings point to alterations in molecular events linked to retinoid X receptor (RXR) signalling, neuronal cell proliferation and migration, cellular stress responses including unfolded protein response, lipid metabolism, and myelination. Exposure to the POP mixture increased methionine oxidation, whereas PFOS decreased oxidation. Several of the altered genes and proteins are involved in a wide variety of neurological disorders. We conclude that POP exposure can interfere with fundamental aspects of neurodevelopment, altering molecular pathways that are associated with adverse neurocognitive and behavioural outcomes.
    Keywords Chicken embryo ; Environmental toxicants ; Neurodevelopment ; Prenatal exposure ; RNA-seq transcriptomics ; Proteomics ; Environmental sciences ; GE1-350
    Subject code 333
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Perinatal exposure to a human relevant mixture of persistent organic pollutants

    Silje Modahl Johanson / Erik Ropstad / Gunn Charlotte Østby / Mona Aleksandersen / Galia Zamaratskaia / Gudrun Seeberg Boge / Ruth Halsne / Cathrine Trangerud / Jan Ludvig Lyche / Hanne Friis Berntsen / Karin Elisabeth Zimmer / Steven Verhaegen

    PLoS ONE, Vol 16, Iss 6, p e

    Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice.

    2021  Volume 0252954

    Abstract: The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to ... ...

    Abstract The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Perinatal exposure to a human relevant mixture of persistent organic pollutants

    Silje Modahl Johanson / Erik Ropstad / Gunn Charlotte Østby / Mona Aleksandersen / Galia Zamaratskaia / Gudrun Seeberg Boge / Ruth Halsne / Cathrine Trangerud / Jan Ludvig Lyche / Hanne Friis Berntsen / Karin Elisabeth Zimmer / Steven Verhaegen

    PLoS ONE, Vol 16, Iss

    Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

    2021  Volume 6

    Abstract: The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to ... ...

    Abstract The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Effects of defined mixtures of POPs and endocrine disruptors on the steroid metabolome of the human H295R adrenocortical cell line

    Ahmed, Kareem Eldin Mohammed / Anders Goksøyr / Erik Ropstad / Hanne Friis Berntsen / Håvard G. Frøysa / Karin Elisabeth Zimmer / Nello Blaser / Odd André Karlsen / Ralf Kellmann / Steven Verhaegen

    Chemosphere. 2019 Mar., v. 218

    2019  

    Abstract: The presence of environmental pollutants in our ecosystem may impose harmful health effects to wildlife and humans. Several of these toxic chemicals have a potential to interfere with the endocrine system. The adrenal cortex has been identified as the ... ...

    Abstract The presence of environmental pollutants in our ecosystem may impose harmful health effects to wildlife and humans. Several of these toxic chemicals have a potential to interfere with the endocrine system. The adrenal cortex has been identified as the main target organ affected by endocrine disrupting chemicals. The aim of this work was to assess exposure effects of defined and environmentally relevant mixtures of chlorinated, brominated and perfluorinated chemicals on steroidogenesis, using the H295R adrenocortical cell line model in combination with a newly developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method. By using this approach, we could simultaneously analyze 19 of the steroids in the steroid biosynthesis pathway, revealing a deeper insight into possible disruption of steroidogenesis. Our results showed a noticeable down-regulation in steroid production when cells were exposed to the highest concentration of a mixture of brominated and fluorinated compounds (10,000-times human blood values). In contrast, up-regulation was observed with estrone under the same experimental condition, as well as with some other steroids when cells were exposed to a perfluorinated mixture (1000-times human blood values), and the mixture of chlorinated and fluorinated compounds. Interestingly, the low concentration of the perfluorinated mixture alone produced a significant, albeit small, down-regulation of pregnenolone, and the total mixture a similar effect on 17-hydroxypregnenolone. Other mixtures resulted in only slight deviations from the control. Indication of synergistic effects were noted when we used a statistical model to improve data interpretation. A potential for adverse outcomes of human exposures is indicated, pointing to the need for further investigation into these mixtures.
    Keywords adrenal cortex ; biosynthesis ; blood ; bromination ; cell lines ; ecosystems ; endocrine-disrupting chemicals ; estrone ; humans ; liquid chromatography ; metabolome ; perfluorocarbons ; pollutants ; pregnenolone ; statistical models ; steroidogenesis ; synergism ; tandem mass spectrometry ; toxic substances ; wildlife
    Language English
    Dates of publication 2019-03
    Size p. 328-339.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 120089-6
    ISSN 1879-1298 ; 0045-6535 ; 0366-7111
    ISSN (online) 1879-1298
    ISSN 0045-6535 ; 0366-7111
    DOI 10.1016/j.chemosphere.2018.11.057
    Database NAL-Catalogue (AGRICOLA)

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