Long-term effects on hypothalamic neuropeptides after developmental exposure to chlorpyrifos in mice.
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.


OBJECTIVE
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.
Tait
Sabrina
S
Section of Food and Veterinary Toxicology, Department of Food Safety and Veterinary Public Health, Rome, Italy.
Ricceri
Laura
L
Venerosi
Aldina
A
Maranghi
Francesca
F
Mantovani
Alberto
A
Calamandrei
Gemma
G
D000818:Animals; D015153:Blotting, Western; D004390:Chlorpyrifos / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007306:Insecticides / Q000633:toxicity*; D018811:Maternal Exposure; D051379:Mice; D009479:Neuropeptides / Q000502:physiology*; D011247:Pregnancy
D007306:Insecticides; D009479:Neuropeptides; D004390:Chlorpyrifos