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  1. Article ; Online: A Human Relevant Defined Mixture of Persistent Organic Pollutants (POPs) Affects In Vitro Secretion of Glucagon-Like Peptide 1 (GLP-1), but Does Not Affect Translocation of Its Receptor.

    Shannon, Maeve / Xie, Yuling / Verhaegen, Steven / Wilson, Jodie / Berntsen, Hanne F / Zimmer, Karin E / Ropstad, Erik / Green, Brian D / Connolly, Lisa

    Toxicological sciences : an official journal of the Society of Toxicology

    2019  Volume 172, Issue 2, Page(s) 359–367

    Abstract: Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of type 2 diabetes and obesity. A complex mixture of 29 POPs (Total mixture), based on human blood concentrations, was used ... ...

    Abstract Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of type 2 diabetes and obesity. A complex mixture of 29 POPs (Total mixture), based on human blood concentrations, was used to expose a glucagon-like peptide 1 (GLP-1) secreting enteroendocrine cell line (pGIP/neo: STC-1) in vitro for 3 and 24 h. Significant increases of GLP-1 occurred when cells were exposed to the Total mixture at ×500 blood levels. Six sub-mixtures representing chlorinated (Cl), brominated (Br), and perfluorinated chemicals (PFAA), and their combinations (Cl + Br, Cl + PFAA, Br + PFAA) were also tested at ×500. Secretion levels seen for these remained lower than the Total mixture, and the Br mixture had no effect. After 24 h, increased secretion was seen with all mixtures at ×1 blood levels. Cytotoxicity was present for ×100 and ×500 blood levels. When tested in a GLP-1 receptor translocation assay (U2OS-GLP1R-EGFP), neither agonistic nor antagonist effects on receptor internalization were seen for any of the mixtures. We conclude individual classes of POPs, alone or in combination, can affect GLP-1 secretion and may contribute as a molecular mechanism linking environmental toxicants and diabetes.
    MeSH term(s) Cell Culture Techniques ; Cell Line ; Cell Survival/drug effects ; Endocrine Disruptors/chemistry ; Endocrine Disruptors/toxicity ; Enteroendocrine Cells/drug effects ; Enteroendocrine Cells/metabolism ; Environmental Pollutants/chemistry ; Environmental Pollutants/toxicity ; Glucagon-Like Peptide 1/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; Humans ; Hydrocarbons, Halogenated/chemistry ; Hydrocarbons, Halogenated/toxicity ; Protein Transport
    Chemical Substances Endocrine Disruptors ; Environmental Pollutants ; GLP1R protein, human ; Glucagon-Like Peptide-1 Receptor ; Hydrocarbons, Halogenated ; Glucagon-Like Peptide 1 (89750-14-1)
    Language English
    Publishing date 2019-08-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420885-4
    ISSN 1096-0929 ; 1096-6080
    ISSN (online) 1096-0929
    ISSN 1096-6080
    DOI 10.1093/toxsci/kfz192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1709: Show issues Location:
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  2. Article ; Online: Maternal exposure to a mixture of persistent organic pollutants (POPs) affects testis histology, epididymal sperm count and induces sperm DNA fragmentation in mice.

    Khezri, Abdolrahman / Lindeman, Birgitte / Krogenæs, Anette K / Berntsen, Hanne F / Zimmer, Karin E / Ropstad, Erik

    Toxicology and applied pharmacology

    2017  Volume 329, Page(s) 301–308

    Abstract: Persistent organic pollutants (POPs) are widespread throughout the environment and some are suspected to induce reproductive toxicity. As animals and humans are exposed to complex mixtures of POPs, it is reasonable to assess how such mixtures could ... ...

    Abstract Persistent organic pollutants (POPs) are widespread throughout the environment and some are suspected to induce reproductive toxicity. As animals and humans are exposed to complex mixtures of POPs, it is reasonable to assess how such mixtures could interact with the reproductive system. Our aim is to investigate how maternal exposure to a mixture of 29 different persistent organic pollutants, formulated to mimic the relative POP levels in the food basket of the Scandinavian population, could alter reproductive endpoints. Female mice were exposed via feed from weaning, during pregnancy and lactation in 3 exposure groups (control (C), low (L) and high (H)). Testicular morphometric endpoints, epididymal sperm concentration and sperm DNA integrity were assessed in adult male offspring. We found that the number of tubules, proportion of tubule compartments and epididymal sperm concentration significantly decreased in both POP exposed groups. Epididymal sperm from both POP exposed groups showed increased DNA fragmentation. It is concluded that maternal exposure to a defined POP mixture relevant to human exposure can affect testicular development, sperm production and sperm chromatin integrity.
    MeSH term(s) Animals ; Chromatin Assembly and Disassembly/drug effects ; DNA Fragmentation ; Environmental Pollutants/toxicity ; Epididymis/drug effects ; Epididymis/metabolism ; Epididymis/pathology ; Female ; Lactation ; Male ; Maternal Exposure/adverse effects ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Organic Chemicals/toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects ; Reproduction/drug effects ; Risk Assessment ; Sex Factors ; Sperm Count ; Spermatozoa/drug effects ; Spermatozoa/metabolism ; Spermatozoa/pathology ; Testis/drug effects ; Testis/metabolism ; Testis/pathology ; Weaning
    Chemical Substances Environmental Pollutants ; Organic Chemicals
    Language English
    Publishing date 2017-08-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 204477-8
    ISSN 1096-0333 ; 0041-008X
    ISSN (online) 1096-0333
    ISSN 0041-008X
    DOI 10.1016/j.taap.2017.06.019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Maternal exposure to a human based mixture of persistent organic pollutants (POPs) affect gene expression related to brain function in mice offspring hippocampus.

    Myhre, Oddvar / Zimmer, Karin E / Hudecova, Alexandra M / Hansen, Kristine E A / Khezri, Abdolrahman / Berntsen, Hanne F / Berg, Vidar / Lyche, Jan L / Mandal, Siddhartha / Duale, Nur / Ropstad, Erik

    Chemosphere

    2021  Volume 276, Page(s) 130123

    Abstract: Male and female mice pups were exposed to a low and high dose of a human relevant mixture of persistent organic pollutants (POPs) during pregnancy and lactation. Most compounds detected in the dams were found in offspring brains. The mice offspring ... ...

    Abstract Male and female mice pups were exposed to a low and high dose of a human relevant mixture of persistent organic pollutants (POPs) during pregnancy and lactation. Most compounds detected in the dams were found in offspring brains. The mice offspring exhibited changed expression of hippocampal genes involved in cognitive function (Adora2a, Auts2, Crlf1, Chrnb2, Gdnf, Gnal, Kcnh3), neuroinflammation (Cd47, Il1a), circadian rhythm (Per1, Clock), redox signalling (Hmox2) and aryl hydrocarbon receptor activation (Cyp1b1). A few genes were differentially expressed in males versus females. Mostly, similar patterns of gene expression changes were observed between the low and high dose groups. Effects on learning and memory function measured in the Barnes maze (not moving, escape latency) were found in the high dose group when combined with moderate stress exposure (air flow from a fan). Mediation analysis indicated adaptation to the effects of exposure since gene expression compensated for learning disabilities (escape latency, walking distance and time spent not moving in the maze). Additionally, random forest analysis indicated that Kcnh3, Gnal, and Crlf1 were the most important genes for escape latency, while Hip1, Gnal and the low exposure level were the most important explanatory factors for passive behaviour (not moving). Altogether, this study showed transfer of POPs to the offspring brains after maternal exposure, modulating the expression level of genes involved in brain function.
    MeSH term(s) Animals ; Brain ; Female ; Gene Expression ; Hippocampus ; Humans ; Male ; Maternal Exposure ; Maze Learning ; Mice ; Persistent Organic Pollutants ; Pregnancy ; Prenatal Exposure Delayed Effects/genetics
    Language English
    Publishing date 2021-03-03
    Publishing country England
    Document type Journal 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.2021.130123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Maternal exposure to a human relevant mixture of persistent organic pollutants reduces colorectal carcinogenesis in A/J Min/+ mice.

    Johanson, Silje M / Swann, Jonathan R / Umu, Özgün C O / Aleksandersen, Mona / Müller, Mette H B / Berntsen, Hanne F / Zimmer, Karin E / Østby, Gunn C / Paulsen, Jan E / Ropstad, Erik

    Chemosphere

    2020  Volume 252, Page(s) 126484

    Abstract: An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to ... ...

    Abstract An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to POPs on colorectal cancer and gut microbiota. This study characterized the influence of exposure to a human relevant mixture of POPs during gestation and lactation on colorectal cancer, intestinal metabolite composition and microbiota in the A/J Min/+ mouse model. Surprisingly, the maternal POP exposure decreased colonic tumor burden, as shown by light microscopy and histopathological evaluation, indicating a restriction of colorectal carcinogenesis.
    MeSH term(s) Animals ; Carcinogenesis ; Carcinogens/metabolism ; Carcinogens/toxicity ; Colonic Neoplasms ; Colorectal Neoplasms/chemically induced ; Environmental Pollutants/metabolism ; Environmental Pollutants/toxicity ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Lactation ; Maternal Exposure/statistics & numerical data ; Metabolomics ; Mice ; Mice, Inbred Strains ; Microbiota ; RNA, Ribosomal, 16S
    Chemical Substances Carcinogens ; Environmental Pollutants ; RNA, Ribosomal, 16S
    Language English
    Publishing date 2020-03-13
    Publishing country England
    Document type Journal 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.2020.126484
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Maternal exposure to a human relevant mixture of persistent organic pollutants reduces colorectal carcinogenesis in A/J Min/+ mice

    Johanson, Silje M / Swann, Jonathan R / Umu, Özgün C.O / Aleksandersen, Mona / Müller, Mette H.B / Berntsen, Hanne F / Zimmer, Karin E / Østby, Gunn C / Paulsen, Jan E / Ropstad, Erik

    Chemosphere. 2020 Mar. 12,

    2020  

    Abstract: An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to ... ...

    Abstract An increased risk of developing colorectal cancer has been associated with exposure to persistent organic pollutants (POPs) and alteration in the gut bacterial community. However, there is limited understanding about the impact of maternal exposure to POPs on colorectal cancer and gut microbiota. This study characterized the influence of exposure to a human relevant mixture of POPs during gestation and lactation on colorectal cancer, intestinal metabolite composition and microbiota in the A/J Min/+ mouse model. Surprisingly, the maternal POP exposure decreased colonic tumor burden, as shown by light microscopy and histopathological evaluation, indicating a restriction of colorectal carcinogenesis. 1H nuclear magnetic resonance spectroscopy-based metabolomic analysis identified alterations in the metabolism of amino acids, lipids, glycerophospholipids and energy in intestinal tissue. In addition, 16S rRNA sequencing of gut microbiota indicated that maternal exposure modified fecal bacterial composition. In conclusion, the results showed that early-life exposure to a mixture of POPs reduced colorectal cancer initiation and promotion, possibly through modulation of the microbial and biochemical environment. Further studies should focus on the development of colorectal cancer after combined maternal and dietary exposures to environmentally relevant low-dose POP mixtures.
    Keywords amino acids ; animal models ; bacterial communities ; carcinogenesis ; colorectal neoplasms ; energy ; histopathology ; humans ; intestinal microorganisms ; intestines ; lactation ; light microscopy ; lipids ; maternal exposure ; metabolism ; metabolites ; metabolomics ; mice ; nuclear magnetic resonance spectroscopy ; persistent organic pollutants ; pregnancy ; ribosomal RNA ; sequence analysis
    Language English
    Dates of publication 2020-0312
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    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.2020.126484
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: A human exposure based mixture of persistent organic pollutants affects the stress response in female mice and their offspring.

    Hudecova, Alexandra M / Hansen, Kristine E A / Mandal, Siddhartha / Berntsen, Hanne F / Khezri, Abdolrahman / Bale, Tracy L / Fraser, Thomas W K / Zimmer, Karin E / Ropstad, Erik

    Chemosphere

    2018  Volume 197, Page(s) 585–593

    Abstract: Persistent organic pollutants (POPs) are found in the food chain of both humans and animals and exert a wide spectrum of potentially adverse effects. The present experiment aimed to investigate whether a defined mixture of 29 POPs, based on the dietary ... ...

    Abstract Persistent organic pollutants (POPs) are found in the food chain of both humans and animals and exert a wide spectrum of potentially adverse effects. The present experiment aimed to investigate whether a defined mixture of 29 POPs, based on the dietary intake of Scandinavians, could affect the stress response in female mice exposed through ingestion, and in their offspring. Female mice 129:C57BL/6F0 hybrids were exposed from weaning, throughout pregnancy, and up until necropsy, to either 5000 × or 100 000 × the estimated daily intake for Scandinavians. The offspring were fed a reference diet containing no POPs. Both the mothers and their offspring were tested for basal and stress responsive corticosterone levels, and in an open field test to measure locomotor activity and anxiety-like behaviours. We found mothers to have elevated basal corticosterone levels, as well as a prolonged stress response following POP exposure. In the offspring, there was no effect of POPs on the stress response in females, but the exposed males had an over-sensitised stress response. There was no effect on behaviour in either the mothers or the offspring. In conclusion, we found a human relevant POP mixture can lead to subtle dysregulation of the hypothalamus-pituitary-adrenal axis in mice. As HPA axis dysregulation is commonly associated with neurological disorders, further studies should explore the relevance of this outcome for humans.
    MeSH term(s) Animals ; Anxiety ; Corticosterone/metabolism ; Environmental Pollutants/toxicity ; Female ; Hypothalamo-Hypophyseal System/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Organic Chemicals/toxicity ; Pituitary-Adrenal System/drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; Stress, Physiological/physiology
    Chemical Substances Environmental Pollutants ; Organic Chemicals ; Corticosterone (W980KJ009P)
    Language English
    Publishing date 2018-04
    Publishing country England
    Document type Journal 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.2018.01.085
    Database MEDical Literature Analysis and Retrieval System OnLINE

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