PMID- 19165396
OWN - NLM
STAT- MEDLINE
DCOM- 20090306
LR  - 20211020
IS  - 0091-6765 (Print)
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Linking)
VI  - 117
IP  - 1
DP  - 2009 Jan
TI  - Long-term effects on hypothalamic neuropeptides after developmental exposure to 
      chlorpyrifos in mice.
PG  - 112-6
LID - 10.1289/ehp.11696 [doi]
AB  - 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.
FAU - Tait, Sabrina
AU  - Tait S
AD  - Section of Food and Veterinary Toxicology, Department of Food Safety and 
      Veterinary Public Health, Rome, Italy.
FAU - Ricceri, Laura
AU  - Ricceri L
FAU - Venerosi, Aldina
AU  - Venerosi A
FAU - Maranghi, Francesca
AU  - Maranghi F
FAU - Mantovani, Alberto
AU  - Mantovani A
FAU - Calamandrei, Gemma
AU  - Calamandrei G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080822
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Insecticides)
RN  - 0 (Neuropeptides)
RN  - JCS58I644W (Chlorpyrifos)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Chlorpyrifos/*toxicity
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Hypothalamus/*drug effects/physiology
MH  - Insecticides/*toxicity
MH  - *Maternal Exposure
MH  - Mice
MH  - Neuropeptides/*physiology
MH  - Pregnancy
PMC - PMC2627853
OTO - NOTNLM
OT  - arginine vasopressin
OT  - developmental neurotoxicity
OT  - endocrine disruptors
OT  - organophosphorus insecticides
OT  - oxytocin
OT  - prolactin
EDAT- 2009/01/24 09:00
MHDA- 2009/03/07 09:00
PMCR- 2009/01/01
CRDT- 2009/01/24 09:00
PHST- 2008/05/13 00:00 [received]
PHST- 2008/08/22 00:00 [accepted]
PHST- 2009/01/24 09:00 [entrez]
PHST- 2009/01/24 09:00 [pubmed]
PHST- 2009/03/07 09:00 [medline]
PHST- 2009/01/01 00:00 [pmc-release]
AID - ehp-117-112 [pii]
AID - 10.1289/ehp.11696 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2009 Jan;117(1):112-6. doi: 10.1289/ehp.11696. Epub 2008 
      Aug 22.