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Long term transcriptional and behavioral effects in mice developmentally exposed to a mixture of endocrine disruptors associated with delayed human neurodevelopment

Repouskou, Anastasia ; Papadopoulou, Anastasia Konstantina ; Panagiotidou, Emily ; Trichas, Panagiotis ; Lindh, Christian LU orcid ; Bergman, Åke ; Gennings, Chris ; Bornehag, Carl Gustaf LU ; Rüegg, Joëlle and Kitraki, Efthymia , et al. (2020) In Scientific Reports 10(1).
Abstract

Accumulating evidence suggests that gestational exposure to endocrine disrupting chemicals (EDCs) may interfere with normal brain development and predispose for later dysfunctions. The current study focuses on the exposure impact of mixtures of EDCs that better mimics the real-life situation. We herein describe a mixture of phthalates, pesticides and bisphenol A (mixture N1) detected in pregnant women of the SELMA cohort and associated with language delay in their children. To study the long-term impact of developmental exposure to N1 on brain physiology and behavior we administered this mixture to mice throughout gestation at doses 0×, 0.5×, 10×, 100× and 500× the geometric mean of SELMA mothers’ concentrations, and examined their... (More)

Accumulating evidence suggests that gestational exposure to endocrine disrupting chemicals (EDCs) may interfere with normal brain development and predispose for later dysfunctions. The current study focuses on the exposure impact of mixtures of EDCs that better mimics the real-life situation. We herein describe a mixture of phthalates, pesticides and bisphenol A (mixture N1) detected in pregnant women of the SELMA cohort and associated with language delay in their children. To study the long-term impact of developmental exposure to N1 on brain physiology and behavior we administered this mixture to mice throughout gestation at doses 0×, 0.5×, 10×, 100× and 500× the geometric mean of SELMA mothers’ concentrations, and examined their offspring in adulthood. Mixture N1 exposure increased active coping during swimming stress in both sexes, increased locomotion and reduced social interaction in male progeny. The expression of corticosterone receptors, their regulator Fkbp5, corticotropin releasing hormone and its receptor, oxytocin and its receptor, estrogen receptor beta, serotonin receptors (Htr1a, Htr2a) and glutamate receptor subunit Grin2b, were modified in the limbic system of adult animals, in a region-specific, sexually-dimorphic and experience-dependent manner. Principal component analysis revealed gene clusters associated with the observed behavioral responses, mostly related to the stress axis. This integration of epidemiology-based data with an experimental model increases the evidence that prenatal exposure to EDC mixtures impacts later life brain functions.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
9367
publisher
Nature Publishing Group
external identifiers
  • scopus:85086169824
  • pmid:32518293
ISSN
2045-2322
DOI
10.1038/s41598-020-66379-x
language
English
LU publication?
yes
id
31c558b9-ca05-4598-b8fa-8e8044e52cbc
date added to LUP
2020-06-26 09:44:58
date last changed
2024-06-12 16:07:30
@article{31c558b9-ca05-4598-b8fa-8e8044e52cbc,
  abstract     = {{<p>Accumulating evidence suggests that gestational exposure to endocrine disrupting chemicals (EDCs) may interfere with normal brain development and predispose for later dysfunctions. The current study focuses on the exposure impact of mixtures of EDCs that better mimics the real-life situation. We herein describe a mixture of phthalates, pesticides and bisphenol A (mixture N1) detected in pregnant women of the SELMA cohort and associated with language delay in their children. To study the long-term impact of developmental exposure to N1 on brain physiology and behavior we administered this mixture to mice throughout gestation at doses 0×, 0.5×, 10×, 100× and 500× the geometric mean of SELMA mothers’ concentrations, and examined their offspring in adulthood. Mixture N1 exposure increased active coping during swimming stress in both sexes, increased locomotion and reduced social interaction in male progeny. The expression of corticosterone receptors, their regulator Fkbp5, corticotropin releasing hormone and its receptor, oxytocin and its receptor, estrogen receptor beta, serotonin receptors (Htr1a, Htr2a) and glutamate receptor subunit Grin2b, were modified in the limbic system of adult animals, in a region-specific, sexually-dimorphic and experience-dependent manner. Principal component analysis revealed gene clusters associated with the observed behavioral responses, mostly related to the stress axis. This integration of epidemiology-based data with an experimental model increases the evidence that prenatal exposure to EDC mixtures impacts later life brain functions.</p>}},
  author       = {{Repouskou, Anastasia and Papadopoulou, Anastasia Konstantina and Panagiotidou, Emily and Trichas, Panagiotis and Lindh, Christian and Bergman, Åke and Gennings, Chris and Bornehag, Carl Gustaf and Rüegg, Joëlle and Kitraki, Efthymia and Stamatakis, Antonios}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Long term transcriptional and behavioral effects in mice developmentally exposed to a mixture of endocrine disruptors associated with delayed human neurodevelopment}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-66379-x}},
  doi          = {{10.1038/s41598-020-66379-x}},
  volume       = {{10}},
  year         = {{2020}},
}