Document Detail


Effect of prenatal peroxisome proliferator-activated receptor alpha (PPARalpha) agonism on postnatal development.
MedLine Citation:
PMID:  20637823     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent work indicates that PPARalpha is required for perfluorooctanoic acid (PFOA)-induced postnatal lethality resulting from prenatal exposure. The present study tested the hypothesis that relatively modest activation of PPARalpha during prenatal development will cause postnatal lethality, similar to that observed with PFOA, a relatively low affinity PPARalpha agonist. Female wild-type and Pparalpha-null mice were mated overnight with males of the same genotype. The presence of a copulatory plug on the morning after mating was indicative of pregnancy and considered gestation day (GD) 0. Plugged female mice were fed either a control diet or one containing clofibrate (0.5%) or Wy-14,643 (0.005%) until GD18 or until parturition. Mice were examined on GD18 or on postnatal day (PND) 20 following the prenatal exposure period. Dietary administration of clofibrate or Wy-14,643 did not affect maternal weight or weight gain, the average number of implantations, the percentage of litter loss, the average number of live/dead fetuses, average crown-rump length, or the average fetal weight on GD18 in either genotype. An increase in relative maternal liver weight and elevated expression of PPARalpha target genes in maternal and fetal livers on GD18 were observed, indicative of PPARalpha-dependent changes in both the maternal and fetal compartments. However, no defects in postnatal development were observed by either clofibrate or Wy-14,643 in either genotype by PND20. These results demonstrate that relatively low level activation of PPARalpha by clofibrate or Wy-14,643 during prenatal development does not cause postnatal lethality.
Authors:
Prajakta S Palkar; Cherie R Anderson; Christina H Ferry; Frank J Gonzalez; Jeffrey M Peters
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-15
Journal Detail:
Title:  Toxicology     Volume:  276     ISSN:  1879-3185     ISO Abbreviation:  Toxicology     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-09-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  79-84     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Veterinary and Biomedical Sciences and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, United States.
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MeSH Terms
Descriptor/Qualifier:
Animals
Clofibrate / pharmacology*
Female
Genotype
Liver / drug effects,  metabolism
Male
Mice
Mice, Knockout
Organ Size / drug effects
PPAR alpha / agonists*,  genetics
Peroxisome Proliferators / pharmacology*
Pregnancy
Prenatal Exposure Delayed Effects
Pyrimidines / pharmacology*
Chemical
Reg. No./Substance:
0/PPAR alpha; 0/Peroxisome Proliferators; 0/Pyrimidines; 50892-23-4/pirinixic acid; 637-07-0/Clofibrate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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