Long-term effects on hypothalamic neuropeptides after developmental exposure to chlorpyrifos in mice
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BACKGROUND: Increasing evidence from animal and human studies indicates that chlorpyrifos (CPF), similar to other organophosphorus insecticides still widely used, is a developmental neurotoxicant. Developmental exposure to CPF in rodents induces sex-dimorphic behavioral changes at adulthood, including social and agonistic responses, which suggests that CPF may interfere with maturation of neuroendocrine mechanisms. OBJECTIVES: We assessed the hypothesis that CPF affects the levels of neurohypophyseal hormones acting as modulators of social behavior in mammals, such as oxytocin (OT), arginine vasopressin (AVP), and prolactin (PRL). METHODS: Pregnant female mice were orally administered with either vehicle (peanut oil) or 3 or 6 mg/kg CPF on gestational day (GD) 15 to GD18, and offspring were treated subcutaneously with either vehicle or 1 or 3 mg/kg CPF on postnatal days (PNDs) 11 to PND14. Dose levels were chosen to avoid systemic toxicity and inhibition of brain acetylcholinesterase. Offspring were sacrificed at 5 months of age, and expression of OT, AVP, and PRL was analyzed in the hypothalamus by Western blot or enzyme-linked immunosorbent assay (ELISA) analysis. RESULTS: Both male and female mice showed dose-related enhancement of OT expression, with males presenting the more intense effect. AVP expression was significantly reduced in male mice at the higher prenatal and postnatal dose. We observed no significant effect on PRL expression in either sex. Overall, outcomes were mainly attributable to fetal exposure, whereas postnatal doses appeared to potentiate the prenatal effects. CONCLUSIONS: Our data indicate that developmental exposure to CPF may permanently interfere with specific key signaling proteins of the hypothalamic peptidergic system, with time-, dose-, and sex-related effects still evident at adulthood.
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In CD1 mice, pre- and/or postnatal CPF exposure resulted in a dose-dependent decrease in hypothalamic AVP at 5 months of age concomitantly with increased OT.
“In CD1 mice, pre- and/or postnatal exposure to CPF resulted in a dose-dependent decrease in hypothalamic AVP at 5 months of age concomitantly with increased OT (67).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [67]
The Methods identify CD1 mice assessed at 5 months, and the Results report a dose-dependent decrease in hypothalamic AVP alongside a dose-related increase in OT. But the AVP decrease was statistically significant only in males at the highest combined prenatal and postnatal doses; postnatal treatment alone had no significant effect. The claim omits those limits and implies a more general effect of pre- and/or postnatal exposure. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn 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 [67]
The CPF-induced decrease in hypothalamic AVP and increase in OT was more pronounced in males than females and following pre- rather than postnatal exposure.
“This outcome was more pronounced in males than females and following pre-, rather than post-, natal exposure.”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [67]
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- Authors
- Tait, S., Ricceri, L., Venerosi, A., Maranghi, F., Mantovani, A., & Calamandrei, G.
- Affiliations
- Section of Food and Veterinary Toxicology, Department of Food Safety and Veterinary Public Health and
- Istituto Superiore di Sanità (IT)
- Corresponding author
- Calamandrei, Gemma
- ORCID
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2008-08-22
- Volume
- 117
- Issue
- 1
- Pages
- 112-116
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC2627853
- OpenAlex
- W2000259457
- Cited by
- 64
- References
- 56
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 7 · 2014: 9 · 2013: 4 · 2012: 3
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 3416 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- Istituto Superiore di Sanità
- National Institutes of Health
- 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, organophosphate insecticides, developmental neurotoxicity, prenatal exposure, postnatal exposure, hypothalamus, oxytocin, vasopressin, prolactin, neurohypophyseal hormones, social behavior, sex differences, dose-response relationship
- MeSH terms
- Animals, Chlorpyrifos, Enzyme-Linked Immunosorbent Assay, Female, Hypothalamus, Insecticides, Neuropeptides, Pregnancy, Blotting, Western, Maternal Exposure, Mice
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