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Metabolic disruption by a human-relevant chemical mixture, triclosan, and tributyltin in larval zebrafish (Danio rerio)
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.ORCID iD: 0000-0002-7389-8849
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Reproductive Biology in Uppsala (CRU).ORCID iD: 0000-0002-5328-6255
Public Health Sciences, Karlstad University.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.ORCID iD: 0000-0002-4590-1211
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Exposure to metabolism disrupting compounds during development may have short- and long-term health consequences. We have studied the effects of a mixture that consists of perfluoroalkyl acids, phthalate monoesters, and triclosan (TCS) on metabolic endpoints in developing zebrafish (Danio rerio). The mixture has previously been negatively associated with birth weight in the Swedish pregnancy cohort SELMA. We also studied one of the mixture components (TCS) and the known obesogen tributyltin (TBT). Water concentrations of the mixture and TCS corresponded to 1, 20, 60, and 100 times the geometrical mean of the gestational week 10 serum concentration in the SELMA women. The fish were exposed from 3 hours post fertilization and effects on metabolic rate were assessed at 2-5 days post fertilization (dpf) and lipid content in the blood, whole-body neutral lipid content, and adiposity were determined at 7 dpf. Exposure to the mixture and TCS altered metabolic rate. The mixture and both single compounds reduced lipid levels in whole-body samples and in the blood. A higher proportion of fish in the mixture- and TBT-exposed groups had visible adipocytes at 7 dpf compared with the control group and a similar tendency was observed in TCS-exposed fish. Our results demonstrate metabolism disrupting properties of the mixture and its component TCS that were similar to those of TBT. The results further indicate that TCS contributes to, but is not solely responsible for, the effect by the mixture.

Keywords [en]
Mixtures, Zebrafish, adipogenesis, Lipid metabolism, Endocrine disrupting chemicals, Triclosan, Tributyltin
National Category
Environmental Sciences Developmental Biology
Identifiers
URN: urn:nbn:se:uu:diva-408801OAI: oai:DiVA.org:uu-408801DiVA, id: diva2:1423279
Available from: 2020-04-14 Created: 2020-04-14 Last updated: 2020-04-17
In thesis
1. Developmental exposure to mixtures of environmental pollutants: Studies on metabolism, developmental processes, and reproductive organs in zebrafish and chicken embryos
Open this publication in new window or tab >>Developmental exposure to mixtures of environmental pollutants: Studies on metabolism, developmental processes, and reproductive organs in zebrafish and chicken embryos
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Humans and wildlife are continuously exposed to mixtures of environmental pollutants. Mixture toxicity can be challenging to predict due to interactions between chemicals and thus whole-mixture approaches are crucial in toxicology. Developing organisms are generally more sensitive to chemical insult than adults and early exposure has been linked to metabolic and reproductive disorders later in life. It is thus imperative to clarify how mixtures of environmental pollutants affect early development.

Within this thesis, consequences of early exposure to human-relevant chemical mixtures have been demonstrated using zebrafish and chicken embryos. The mixtures were designed previously based on negative associations with birth weight (mixture G) or anogenital distance (mixture S) in Swedish children. Mixture G consist of phthalate monoesters, perfluoroalkyl acids, and triclosan (TCS). It was assessed for effects on developmental processes (apoptosis and wnt/β-catenin signaling) and lipid metabolism in zebrafish. Two components of mixture G were assessed as single compounds: perfluorooctane sulfonate (PFOS) and TCS. Exposure to mixture G induced apoptosis, reduced wnt/β-catenin signalling, increased visceral adiposity, and reduced blood- and whole body-lipid levels in developing zebrafish. PFOS induced apoptosis but not Wnt/β-catenin signaling and TCS had similar effects on lipid levels as the mixture, although the effect of TCS on adipogenesis was not as pronounced. Mixture S, which consists of four phthalate monoesters, and a suggested bisphenol A metabolite (4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene; MBP) were assessed for disruption of reproductive organ development in chicken embryos. No effects were observed by mixture S. MBP caused feminization in male embryos (left ovotestis, feminized gonadal mRNA expression pattern, and Müllerian duct retention). MBP-exposed females displayed smaller left ovaries, malformed left Müllerian ducts, and right Müllerian duct retention.

In conclusion, a mixture that has been implicated in altered intrauterine metabolism and growth in Swedish children caused developmental and metabolism disrupting effects in larval zebrafish. PFOS and TCS most likely contribute to the effects by the mixture. Furthermore, the suggested bisphenol A metabolite MBP, but not a mixture of phthalate monoesters, altered both male and female reproductive organ development in chicken embryos. The results were generated using models of both environmental and human relevance. The results in this thesis demonstrate the value of combining epidemiological and experimental studies to assess mixture toxicity. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 57
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1937
Keywords
Mixtures, Developmental toxicology, Endocrine disrupting chemicals, Metabolism, Feminization, Zebrafish, Chicken embryo
National Category
Pharmacology and Toxicology Environmental Sciences Developmental Biology
Research subject
Biology with specialization in Environmental Toxicology; Biology with specialization in Environmental Toxicology; Biology with specialization in Environmental Toxicology; Biology with specialization in Environmental Toxicology
Identifiers
urn:nbn:se:uu:diva-409018 (URN)978-91-513-0954-5 (ISBN)
Public defence
2020-06-10, Ekmansalen, Evolutionsbiologiskt centrum, Norbyvägen 14, Uppsala, 13:00 (English)
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Supervisors
Available from: 2020-05-19 Created: 2020-04-17 Last updated: 2020-06-16

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Mentor, AnnaMattsson, AnnaBrunström, BjörnJönsson, Maria

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