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Cited by 61Pesticide Exposure and ToxicityNeuroendocrine regulation and behaviorEffects and risks of endocrine disrupting chemicals

Effects of maternal chlorpyrifos diet on social investigation and brain neuroendocrine markers in the offspring – a mouse study

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Venerosi, Aldina, Tait, Sabrina, Stecca, Laura, Chiarotti, Flavia, De Felice, Alessia, Cometa, Maria Francesca, Volpe, Maria Teresa, Calamandrei, Gemma +1 more·2015·Environmental Health
DOI 10.1186/s12940-015-0019-6PMC PMC4448273
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Abstract

BACKGROUND: Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides worldwide. Epidemiological studies on pregnant women and their children suggest a link between in utero CPF exposure and delay in psychomotor and cognitive maturation. A large number of studies in animal models have shown adverse effects of CPF on developing brain and more recently on endocrine targets. Our aim was to determine if developmental exposure to CPF affects social responsiveness and associated molecular neuroendocrine markers at adulthood. METHOD: Pregnant CD1 outbred mice were fed from gestational day 15 to lactation day 14 with either a CPF-added (equivalent to 6 mg/kg/bw/day during pregnancy) or a standard diet. We then assessed in the offspring the long-term effects of CPF exposure on locomotion, social recognition performances and gene expression levels of selected neurondocrine markers in amygdala and hypothalamus. RESULTS: No sign of CPF systemic toxicity was detected. CPF induced behavioral alterations in adult offspring of both sexes: CPF-exposed males displayed enhanced investigative response to unfamiliar social stimuli, whereas CPF-exposed females showed a delayed onset of social investigation and lack of reaction to social novelty. In parallel, molecular effects of CPF were sex dimorphic: in males CPF increased expression of estrogen receptor beta in hypothalamus and decreased oxytocin expression in amygdala; CPF increased vasopressin 1a receptor expression in amygdala in both sexes. CONCLUSIONS: These data indicate that developmental CPF affects mouse social behavior and interferes with development of sex-dimorphic neuroendocrine pathways with potential disruptive effects on neuroendocrine axes homeostasis. The route of exposure selected in our study corresponds to relevant human exposure scenarios, our data thus supports the view that neuroendocrine effects, especially in susceptible time windows, should deserve more attention in risk assessment of OP insecticides.

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  • CPF exposure effects on OT and AVP mRNA expression in the amygdala and hypothalamus were reported.

    “The same group subsequently reported effects on OT and AVP mRNA expression in the amygdala as well as the hypothalamus (68).”

    From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [68]

    The Results section reports decreased Oxt mRNA expression in the amygdala of CPF-exposed males, supporting that part of the claim. It reports an amygdalar increase in AvpR1a (a vasopressin receptor), not Avp mRNA, and explicitly reports no CPF-related difference in hypothalamic Oxt or Avp mRNA expression. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • In both studies, CPF-exposed mice displayed altered social and exploratory behaviors, with specific outcomes differing by sex.

    “In both studies CPF-exposed mice displayed altered social and exploratory behaviors, with the specific outcomes differing by sex.”

    From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [68]

    The Results (Social recognition; page unavailable) report altered social investigation in CPF-exposed offspring, with different patterns in males and females. But the Results (Open field; page unavailable) report no CPF effect on spontaneous behavior, so this study does not support the claim that exploratory behavior was altered. This paper also cannot establish what occurred in the other study referenced by “both studies.” (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • ERβ was upregulated in the male hypothalamus following CPF exposure.

    “Notably, ERβ was also found to be upregulated in the male hypothalamus.”

    From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [68]

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Research works printed but not linked: 59

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Authors
Venerosi, A., Tait, S., Stecca, L., Chiarotti, F., De Felice, A., Cometa, M. F., Volpe, M. T., Calamandrei, G., & Ricceri, L.
Affiliations
Istituto Superiore di Sanità (IT)
Corresponding author
Ricceri, Laura
ORCID
Venue
Environmental Health
Publisher
Springer Science and Business Media LLC
Published
2015-04-02
Volume
14
Issue
1
Pages
32-32
ISSN
1476-069X (ISSN-L)
DOI
10.1186/s12940-015-0019-6
PMC
PMC4448273
OpenAlex
W2006072723
Cited by
61
References
68
Citations by year
2026: 3 · 2025: 7 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 8 · 2017: 5 · 2016: 4 · 2015: 3
FWCI
8.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Health (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
Funders
European Commission (603946)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords
chlorpyrifos, organophosphorus pesticides, prenatal pesticide exposure, developmental neurotoxicity, social investigation, social recognition, social novelty, sex differences, neuroendocrine markers, estrogen receptor beta, oxytocin, vasopressin 1a receptor, amygdala, hypothalamus, locomotion
MeSH terms
Acetylcholinesterase, Amygdala, Animals, Chlorpyrifos, Female, Hypothalamus, Insecticides, Male, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, Estrogen, Social Behavior, Biomarkers, Gene Expression, Receptors, Vasopressin, Receptors, Oxytocin, Maternal Exposure, Recognition, Psychology, Mice

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