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Publication : A species difference in the peroxisome proliferator-activated receptor α-dependent response to the developmental effects of perfluorooctanoic acid.

First Author  Albrecht PP Year  2013
Journal  Toxicol Sci Volume  131
Issue  2 Pages  568-82
PubMed ID  23143925 Mgi Jnum  J:192820
Mgi Id  MGI:5466620 Doi  10.1093/toxsci/kfs318
Citation  Albrecht PP, et al. (2013) A Species Difference in the Peroxisome Proliferator-Activated Receptor alpha-Dependent Response to the Developmental Effects of Perfluorooctanoic Acid. Toxicol Sci 131(2):568-82
abstractText  This study examined the effect of prenatal perfluorooctanoic acid (PFOA) administration on pre- and postnatal development using peroxisome proliferator-activated receptor alpha (PPARalpha)-humanized mice to determine if species differences in receptor activity might influence the developmental effects induced by PFOA. Pregnant mice were treated daily with water or PFOA (3mg/kg) by po gavage from gestation day 1 (GD1) until GD17 and then either euthanized on GD18 or allowed to give birth and then euthanized on postnatal day 20 (PND20). No changes in average fetal weight, crown-to-rump length, or placental weight were observed on GD18. Expression of mRNA encoding the PPARalpha target genes acyl CoA oxidase (Acox1) and cytochrome P450 4a10 (Cyp4a10) in maternal and fetal liver was increased on GD18 in wild-type and PPARalpha-humanized mice but not in Pparalpha-null mice. On PND20, relative liver weight was higher in wild-type mice but not in Pparalpha-null mice or PPARalpha-humanized mice. Hepatic expression of Acox1 and Cyp4a10 mRNA was higher in wild-type mice but not in Pparalpha-null mice or PPARalpha-humanized mice on PND20. The percentage of mice surviving postnatally was lower in wild-type litters but not in litters from Pparalpha-null mice or PPARalpha-humanized mice. No changes in pup weight gain, onset of eye opening, or mammary gland development were found in any genotype. Results from these studies demonstrate that the developmental/postnatal effects resulting from prenatal PFOA exposure in mice are differentially mediated by mouse and human PPARalpha.
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