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A human-relevant mi...
A human-relevant mixture of endocrine disrupting chemicals induces changes in hippocampal DNA methylation correlating with hyperactive behavior in male mice
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- Di Criscio, Michela (författare)
- Uppsala universitet,Fysiologi och miljötoxikologi
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- Lodahl, Jennifer Ekholm (författare)
- Uppsala universitet,Fysiologi och miljötoxikologi
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- Stamatakis, Antonios (författare)
- National and Kapodistrian University of Athens (NKUA), Greece,Natl & Kapodistrian Univ Athens NKUA, Fac Nursing, Sch Hlth Sci, Biol Biochem Lab, Athens 11527, Greece.
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- Kitraki, Efthymia (författare)
- National and Kapodistrian University of Athens (NKUA), Greece,NKUA, Fac Dent, Sch Hlth Sci, Basic Sci Lab, Athens 15272, Greece.
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- Bakoyiannis, Ioannis (författare)
- National and Kapodistrian University of Athens (NKUA), Greece,Natl & Kapodistrian Univ Athens NKUA, Fac Nursing, Sch Hlth Sci, Biol Biochem Lab, Athens 11527, Greece.
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- Repouskou, Anastasia (författare)
- National and Kapodistrian University of Athens (NKUA), Greece,NKUA, Fac Dent, Sch Hlth Sci, Basic Sci Lab, Athens 15272, Greece.
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- Bornehag, Carl-Gustaf, 1957- (författare)
- Karlstads universitet,Institutionen för hälsovetenskaper (from 2013),Karlstad Univ, Fac Hlth Sci & Technol, Dept Hlth Sci, SE-65188 Karlstad, Sweden.
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- Gennings, Chris (författare)
- Icahn School of Medicine at Mount Sinai, USA,Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
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- Lupu, Diana (författare)
- Uppsala universitet,Fysiologi och miljötoxikologi
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- Rüegg, Joëlle (författare)
- Uppsala universitet,Fysiologi och miljötoxikologi
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- Engelska.
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 313
- Relaterad länk:
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https://doi.org/10.1...
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https://kau.diva-por... (primary) (Raw object)
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Humans are ubiquitously exposed to endocrine disrupting chemicals (EDCs), substances that interfere with endogenous hormonal signaling. Exposure during early development is of particular concern due to the programming role of hormones during this period. A previous epidemiological study has shown association between prenatal co-exposure to 8 EDCs (Mixture N1) and language delay in children, suggesting an effect of this mixture on neurodevelopment. Furthermore, in utero exposure to Mixture N1 altered gene expression and behavior in adult mice. In this study, we investigated whether epigenetic mechanisms could underlie the long term effects of Mixture N1 on gene expression and behavior. To this end, we analyzed DNA methylation at regulatory regions of genes whose expression was affected by Mixture N1 in the hippocampus of in utero exposed mice using bisulfite-pyrosequencing. We show that Mixture N1 decreases DNA methylation in males at three genes that are part of the hypothalamus-pituitary-adrenal (HPA) axis: Nr3c1, Nr3c2, and Crhr1, coding for the glucocorticoid receptor, the mineralocorticoid receptor, and the corticotropin releasing hormone receptor 1, respectively. Furthermore, we show that the decrease in Nr3c1 methylation correlates with increased gene expression, and that Nr3c1, Nr3c2, and Crhr1 methylation correlates with hyperactivity and reduction in social behavior. These findings indicate that an EDC mixture corresponding to a human exposure scenario induces epigenetic changes, and thus programming effects, on the HPA axis that are reflected in the behavioral phenotypes of the adult male offspring.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Alkylation
- Behavioral research
- Brain
- DNA
- Endocrine disrupters
- Gene expression
- Hormones
- Mammals
- Chemical mixtures
- DNA Methylation
- Endocrine disrupting chemicals
- Exposed to
- Genes expression
- Hippocampus
- Human relevant mixture
- Hyperactive behavior
- Hypothalamus-pituitary-adrenal axis
- Male mouse
- Methylation
- adult
- DNA
- endocrine disruptor
- gene expression
- hormone
- male
- methylation
- Public Health Science
- Folkhälsovetenskap
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Di Criscio, Mich ...
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Lodahl, Jennifer ...
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Stamatakis, Anto ...
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Kitraki, Efthymi ...
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Bakoyiannis, Ioa ...
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Repouskou, Anast ...
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Bornehag, Carl-G ...
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Gennings, Chris
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Lupu, Diana
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Rüegg, Joëlle
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Chemosphere
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Karlstads universitet
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Uppsala universitet